AFAP1L1 (Actin Filament-Associated Protein 1-Like 1) – Function and Significance

Gene Overview and Domain Architecture

AFAP1L1 is a human gene encoding an actin-binding adaptor protein of the AFAP family. It was identified based on sequence homology to AFAP1 (Actin Filament-Associated Protein 1), a known 110 kDa actin cross-linker and c-Src kinase binding partner (pmc.ncbi.nlm.nih.gov). AFAP1L1 shares a similar modular domain structure with AFAP1, including an N-terminal Src homology 3 (SH3)-binding motif, one or more SH2-binding motifs, two pleckstrin homology (PH) domains, a central serine-rich segment, a coiled-coil leucine zipper region, and a C-terminal actin filament-binding domain (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The human AFAP1L1 gene is located on chromosome 5q33.1 and encodes a protein of ~768 amino acids (pmc.ncbi.nlm.nih.gov). Notably, both AFAP1L1 and AFAP1 contain the conserved leucine zipper and actin-binding domains needed for self-association and F-actin binding (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). However, subtle sequence differences (especially at the N- and C-termini) suggest AFAP1L1 may have distinct interaction partners and functional nuances compared to AFAP1 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In UniProt, AFAP1L1 is described as “Actin filament-associated protein 1-like 1”, reflecting its similarity to AFAP1 and presumed role in actin cytoskeletal dynamics (UniProt Q8TED9).

Adaptor Function and Actin Association

AFAP1L1 is classified as an adaptor protein – a non-enzymatic scaffolding molecule that links components of signaling pathways or structural complexes (pmc.ncbi.nlm.nih.gov). Like AFAP1, AFAP1L1 can bind directly to actin filaments via its C-terminal actin-binding domain (pmc.ncbi.nlm.nih.gov). In cultured cells, GFP-tagged AFAP1L1 was observed to “decorate” F-actin filaments throughout the cytoplasm (pmc.ncbi.nlm.nih.gov). This actin association, together with its leucine zipper–mediated self-oligomerization, suggests AFAP1L1 can cross-link actin filaments or alter filament architecture, similar to AFAP1’s known actin cross-linking activity (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Indeed, overexpression of AFAP1L1 can induce podosome/invadopodium formation – dynamic actin-rich adhesion structures – even without external stimulation (pmc.ncbi.nlm.nih.gov). In one study, introducing AFAP1L1 into smooth muscle cells triggered robust podosome assembly and localization of AFAP1L1 to these F-actin puncta (pmc.ncbi.nlm.nih.gov). These findings indicate AFAP1L1 is an important cytoskeletal regulator that can drive actin reorganization and specialized invasive structures.

Importantly, AFAP1L1’s binding preferences distinguish it from AFAP1. AFAP1 is known to activate the proto-oncogene kinase c-Src by binding its SH3 domain, but AFAP1L1 does not efficiently bind c-Src (pmc.ncbi.nlm.nih.gov). Instead, AFAP1L1’s N-terminal proline-rich sequence preferentially binds the SH3 domain of cortactin, an actin-regulatory protein (pmc.ncbi.nlm.nih.gov). Cortactin is an Arp2/3 complex scaffold involved in actin branching at lamellipodia and invadopodia, and AFAP1L1’s ability to bind cortactin means it can couple directly to actin polymerization sites. Consistent with this, AFAP1L1 co-localizes with cortactin at cortical actin structures and invadosomes (pmc.ncbi.nlm.nih.gov). In summary, AFAP1L1 functions as a linker between actin filaments and multiple signaling or structural proteins, enabling it to influence the assembly of actin networks and cellular architecture.

Key Interaction Partners and Pathways

As an adaptor, AFAP1L1 interacts with several proteins to mediate its effects on cell structure and signaling:

• Actin Filaments (F-actin): AFAP1L1 directly binds filamentous actin via a C-terminal domain, decorating actin stress fibers and cortical filaments (pmc.ncbi.nlm.nih.gov). This interaction is crucial to its role in cytoskeletal remodeling. AFAP1L1 (and AFAP1) each contain a conserved actin-binding domain sufficient for F-actin binding (pmc.ncbi.nlm.nih.gov). By oligomerizing through its leucine zipper, AFAP1L1 can cross-link actin filaments or scaffold actin with other proteins (pmc.ncbi.nlm.nih.gov).

• Cortactin: AFAP1L1 contains an N-terminal SH3-binding motif that binds strongly to cortactin’s SH3 domain (pmc.ncbi.nlm.nih.gov). Unlike AFAP1 (which binds c-Src but not cortactin), AFAP1L1 is efficient at cortactin binding (pmc.ncbi.nlm.nih.gov). Through this interaction, AFAP1L1 targets cortactin (and associated Arp2/3 actin-nucleation complexes) to sites of actin assembly. AFAP1L1 and cortactin co-localize in invadopodia/podosomes, and AFAP1L1 overexpression leads to punctate actin–cortactin structures characteristic of these organelles (pmc.ncbi.nlm.nih.gov). This suggests AFAP1L1 helps recruit or stabilize cortactin at actin-rich protrusions, promoting actin polymerization and invasive membrane structures (pmc.ncbi.nlm.nih.gov).

• Vinculin: Vinculin is a mechanosensitive actin-binding protein found in focal adhesions and invadopodial rings. AFAP1L1 was identified as a novel vinculin-binding partner via co-immunoprecipitation (pmc.ncbi.nlm.nih.gov). In carcinoma cells, AFAP1L1 co-localizes with vinculin in ring-like invadopodial adhesion structures (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Notably, forced AFAP1L1 expression causes vinculin to detach from focal adhesions and redistribute to actin-rich puncta (pmc.ncbi.nlm.nih.gov). AFAP1L1-transfected cells show disassembly of normal focal adhesion complexes (marked by vinculin and paxillin) and formation of dot-like adhesions at the cell periphery (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This phenotype mimics cells lacking vinculin, which become more rounded and migratory (pmc.ncbi.nlm.nih.gov). The AFAP1L1–vinculin interaction is proposed to negatively modulate vinculin’s function in stabilizing adhesions (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). By sequestering or altering vinculin-containing complexes, AFAP1L1 may reduce adhesion strength and promote a more motile, invasive cell state (pmc.ncbi.nlm.nih.gov). Indeed, AFAP1L1 expression confers resistance to anoikis (detachment-induced apoptosis) in cancer cells, partly through its vinculin-related effects on cell-matrix adhesion (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

• VAV2 and CDC42: Recent research uncovered a connection between AFAP1L1 and Rho-family GTPase signaling in the context of cancer. AFAP1L1 physically associates with VAV2, a guanine nucleotide exchange factor (GEF) that activates Rac1/CDC42 (translational-medicine.biomedcentral.com). In gastric cancer cells, co-immunoprecipitation confirmed an AFAP1L1–VAV2 complex, and this interaction proved functionally significant (translational-medicine.biomedcentral.com). AFAP1L1 recruits or activates VAV2, leading to enhanced activation of the GTPase CDC42 (but not Rac1 or RhoA) (translational-medicine.biomedcentral.com) (translational-medicine.biomedcentral.com). Active CDC42 triggers downstream signaling that includes the integrin α5 (ITGA5) pathway (translational-medicine.biomedcentral.com). Specifically, AFAP1L1 upregulates ITGA5 expression and promotes cell adhesion to collagen/fibronectin in a CDC42- and VAV2-dependent manner (translational-medicine.biomedcentral.com) (translational-medicine.biomedcentral.com). This axis (AFAP1L1–VAV2–CDC42–ITGA5) drives epithelial–mesenchymal transition (EMT) and invasive behavior in gastric cancer models (translational-medicine.biomedcentral.com) (translational-medicine.biomedcentral.com). Notably, AFAP1L1 lacks intrinsic enzymatic activity, so its influence on ITGA5 transcription is indirect, mediated by partnering with VAV2 and downstream signaling cascades (translational-medicine.biomedcentral.com) (translational-medicine.biomedcentral.com).

• c-Src Kinase: Unlike its paralog AFAP1, AFAP1L1 does not strongly bind the Src-family tyrosine kinases. AFAP1 contains tandem SH3-binding motifs that avidly bind c-Src’s SH3 domain (activating Src when AFAP1 is phosphorylated by PKC) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). AFAP1L1, by contrast, has sequence deviations in its SH3 motif that prevent efficient c-Src binding (pmc.ncbi.nlm.nih.gov). As a result, AFAP1L1 is not known to directly activate Src, and its cellular roles appear to diverge from the AFAP1–Src signaling axis. This distinction underscores that AFAP1L1 occupies a different signaling niche, interacting with cortactin and vinculin rather than functioning as a c-Src activator (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). By engaging alternative partners, AFAP1L1 may subserve unique functions in actin remodeling and invasion that complement or differ from AFAP1’s Src-mediated pathways (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Cellular Localization and Expression Patterns

Inside the cell, AFAP1L1 is predominantly a cytosolic, cytoskeleton-associated protein. It localizes along actin stress fibers and cortical microfilaments under basal conditions (pmc.ncbi.nlm.nih.gov). Upon stimulation or overexpression, AFAP1L1 concentrates in punctate F-actin structures such as podosomes and invadopodia, where it co-localizes with actin regulators (e.g. cortactin and Arp2/3 complex) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In cells forming invadopodia, AFAP1L1 and proteins like vinculin and Tks5 form a distinctive ring around the F-actin/cortactin core of the invadopodium (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This ring localization places AFAP1L1 at the interface of the actin core and adhesion machinery, consistent with its role in linking actin filaments to membrane anchors. Notably, AFAP1L1 is capable of translocating to nascent podosomes even without external cues, as shown by its ability to induce podosome assembly autonomously when overexpressed (pmc.ncbi.nlm.nih.gov). This indicates AFAP1L1 can actively drive its own relocalization to sites of actin remodeling.

At the tissue level, AFAP1L1 is broadly expressed in human tissues, often overlapping with AFAP1 but with some distinct patterns (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Immunohistochemical studies found both AFAP1L1 and AFAP1 in many cell types (e.g. endothelial cells of microvasculature, intestinal epithelium, smooth muscle) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). However, AFAP1L1 shows unique enrichment in certain tissues. For example, in skeletal muscle and in the dentate nucleus of the cerebellum, AFAP1L1 was abundant whereas AFAP1 was not detected (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In the brain, AFAP1L1 immunoreactivity was observed around Purkinje cells and granule cell layers of the cerebellum, extending along neuronal fiber tracts (mossy/climbing fibers), whereas AFAP1 localized more to blood vessels and glial cells (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This differential distribution suggests that AFAP1L1 may serve specialized roles in certain muscular or neural contexts – possibly related to actin structures in those cell types – where AFAP1 cannot compensate. Nonetheless, in most tissues AFAP1L1 coexists with AFAP1, indicating a complementary function. Both proteins tend to associate with contractile or motile cell structures (e.g. myoepithelial cells in breast ducts, intestinal smooth muscle, etc.), consistent with involvement in cytoskeletal support and cell movement (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Overall, AFAP1L1’s localization – both subcellular and tissue-level – aligns with its role as an actin-linked adaptor in cells that undergo shape change, adhesion, and migration.

Roles in Cytoskeletal Remodeling and Invadopodia Formation

Evidence to date indicates that AFAP1L1 is a promoter of actin cytoskeletal dynamics, particularly in the context of invasive structures. The protein’s ability to induce podosomes (in vascular smooth muscle cells and other mesenchymal cells) is one clear example (pmc.ncbi.nlm.nih.gov). Podosomes and invadopodia are actin-driven protrusions that mediate extracellular matrix degradation and cell invasion. They consist of a core of polymerized actin (nucleated by Arp2/3, cortactin, N-WASp, etc.) and an adhesion ring containing integrins, vinculin, paxillin, and scaffolds like Tks5. AFAP1L1 participates in both compartments: it binds core components (actin, cortactin) and ring components (vinculin, Tks5) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). AFAP1L1 concentrates at the invadopodial ring together with vinculin and paxillin, while cortactin and F-actin fill the core (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). By bridging these elements, AFAP1L1 likely helps stabilize the invadopodium and link the force-generating actin core to the adhesive contacts on the ECM. Importantly, AFAP1L1 is not just a passive component – it can actively trigger invadopodium formation. Snyder et al. (2011) reported that AFAP1L1 overexpression in fibroblasts or smooth muscle cells spontaneously caused numerous podosome/invadopodium structures to form, even in the absence of typical stimuli like phorbol ester or Src activation (pmc.ncbi.nlm.nih.gov). The induced structures contained AFAP1L1 and cortactin, mirroring native invadosomes (pmc.ncbi.nlm.nih.gov). This suggests AFAP1L1 can initiate the cascading assembly of actin, Arp2/3, and adhesion proteins needed for an invadopodium. Mechanistically, one model is that AFAP1L1 oligomers might cross-link actin filaments at the cortex and simultaneously recruit cortactin via its SH3-binding motif, seeding an actin core. Concurrently, AFAP1L1’s interaction with vinculin and other focal adhesion proteins may reorganize those proteins into a ring around the core. In support of this, Takahashi et al. (2014) found that introducing AFAP1L1 into carcinoma cells disrupted stress fibers and focal adhesions, shifting the cells to a punctate adhesion pattern with high motility (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Essentially, AFAP1L1 drives a transition from stable focal adhesions and bundled actin (characteristic of non-migratory cells) to dynamic adhesive rings and dendritic actin (characteristic of invasive cells). This function aligns with AFAP1L1’s hypothesized physiological role: facilitating cytoskeletal turnover and cell invasiveness. Researchers have hypothesized that AFAP1L1 “may play a similar role to AFAP1 in affecting changes in actin filaments and bridging interactions with binding partners,” but through unique interactions that make it especially adept at promoting invadosome formation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In summary, AFAP1L1 acts as a cytoskeletal “hub” protein that can remodel actin structures and adhesion sites to favor cellular movement and invasion.

Emerging Role in Angiogenesis and Endothelial Tip Cells (YAP–Notch Signaling)

Beyond cancer cell invasiveness, new research has implicated AFAP1L1 in pathological angiogenesis (the formation of new blood vessels in disease settings). A 2023 study found that AFAP1L1 is induced by hypoxia via HIF-1α and highly expressed in endothelial “tip cells” of sprouting blood vessels (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Tip cells lead new capillary sprouts and are characterized by active filopodial protrusions and dynamic actin. AFAP1L1’s actin remodeling ability may thus be important in these cells. Single-cell RNA sequencing and immunofluorescence showed AFAP1L1 is enriched in tip endothelial cells, co-localizing with known tip-cell markers in retinal vasculature models (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Gene ontology and gene set enrichment analyses further linked AFAP1L1 expression to angiogenic processes (sprouting, endothelial cell migration, VEGF signaling) across multiple tumor types (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Functionally, silencing AFAP1L1 had a profound anti-angiogenic effect: in cultured human endothelial cells (HUVECs), AFAP1L1 knockdown impaired cell migration, filopodia formation, and tube-forming capacity, especially under hypoxic conditions (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In a 3D spheroid assay, endothelial cells lacking AFAP1L1 formed significantly shorter and fewer sprouts, indicating reduced angiogenic outgrowth (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Concomitantly, loss of AFAP1L1 upregulated DLL4 (Delta-like ligand 4) expression and enhanced Notch signaling (reflected by increased NICD and HES1 levels, markers of Notch activity) (pmc.ncbi.nlm.nih.gov). DLL4 is a tip-cell-expressed Notch ligand that normally provides lateral inhibition to limit neighboring tip cell formation. The data suggest that AFAP1L1 helps maintain a pro-sprouting state in tip cells by modulating the YAP–DLL4–Notch signaling axis (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). YAP (Yes-associated protein) is a mechanotransduction regulator activated by cytoskeletal tension; it promotes tip cell migration and represses DLL4 to allow sprouting. The 2023 study proposes that AFAP1L1, by organizing the actin cytoskeleton, enables YAP activation in hypoxic endothelial cells, thereby suppressing DLL4 and Notch signaling to favor angiogenesis (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In support of this model, AFAP1L1 knockdown phenocopied excessive Notch activity (high DLL4, reduced sprouting), and this could be rescued by simultaneous DLL4 inhibition (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In vivo, the knockdown of AFAP1L1 in a tumor xenograft led to significantly reduced tumor vascularization and slower tumor growth compared to controls (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Similarly, in a mouse model of retinal neovascular disease, silencing AFAP1L1 suppressed pathological blood vessel formation (as measured by reduced isolectin-stained neovessels) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Collectively, these findings highlight a novel role for AFAP1L1 in driving angiogenic sprouting under hypoxic or diseased conditions. AFAP1L1 links cytoskeletal dynamics to the YAP-Notch pathway in endothelial cells, representing a potential target for anti-angiogenic therapies beyond the conventional VEGF/VEGFR targets (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

AFAP1L1 in Cancer Progression and Metastasis

AFAP1L1 is increasingly recognized as a pro-metastatic factor in cancer. Multiple studies have found that this gene is upregulated in tumors and linked to more aggressive cancer phenotypes. Key evidence from recent research includes:

• Spindle Cell Sarcomas: AFAP1L1 was initially identified as a top metastasis-associated gene in an expression profiling of 65 spindle cell sarcomas (pubmed.ncbi.nlm.nih.gov). High AFAP1L1 mRNA levels were strongly predictive of distant metastasis (multivariate analysis P = 0.0001) (pubmed.ncbi.nlm.nih.gov). This was confirmed in an independent cohort of 41 tumors by quantitative PCR. Patients whose tumors lacked AFAP1L1 protein had significantly better metastasis-free survival, whereas AFAP1L1-positive tumors were prone to metastasize (P = 0.0093, log-rank test) (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Functional assays supported a causal role: knockdown of AFAP1L1 in sarcoma cells reduced cell invasion, while ectopic AFAP1L1 expression in benign mesenchymal cells induced anchorage-independent growth and increased invasiveness with heightened matrix metalloproteinase activity (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Moreover, sarcoma cells overexpressing AFAP1L1 formed larger, faster-growing tumors in mice (pubmed.ncbi.nlm.nih.gov). These results demonstrate that AFAP1L1 actively drives tumor cell invasion and growth in sarcomas, in line with its function as an actin-regulatory adaptor. The authors concluded that “AFAP1L1 has a role in the progression of spindle cell sarcomas and is a prognostic biomarker” for metastasis (pubmed.ncbi.nlm.nih.gov).

• Colorectal Cancer (CRC): In colorectal cancers, AFAP1L1 expression is frequently elevated in tumor tissue compared to normal mucosa (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Takahashi et al. reported upregulation of AFAP1L1 mRNA in 19 of 33 (58%) CRC tumors relative to patient-matched normal colon, as measured by quantitative RT-PCR (pmc.ncbi.nlm.nih.gov). Importantly, high AFAP1L1 levels correlated with disease recurrence. In rectal cancer patients, AFAP1L1 expression status was found to be an independent predictor of postoperative recurrence on multivariate analysis (pmc.ncbi.nlm.nih.gov). Patients with AFAP1L1-high tumors had significantly higher recurrence rates, even when controlling for other factors. Moreover, combining AFAP1L1 expression with lymph node metastasis status improved the accuracy of recurrence risk stratification (pmc.ncbi.nlm.nih.gov). These data suggest AFAP1L1 could serve as a prognostic biomarker in CRC. At the cellular level, AFAP1L1 appears to enhance motility and survival of CRC cells. AFAP1L1-transduced colon cancer cells adopted a rounded, amoeboid shape with increased motility and anoikis resistance in vitro, consistent with a metastatic phenotype (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In vivo, CRC cells overexpressing AFAP1L1 showed accelerated tumor growth in mice, presumably due to their enhanced survival and invasive capacity (pmc.ncbi.nlm.nih.gov). These findings align with AFAP1L1’s known effects on focal adhesions and the cytoskeleton – by loosening adhesion (via vinculin displacement) and promoting invadopodia, AFAP1L1 endows CRC cells with greater invasive potential.

• Gastric Cancer (GC): A comprehensive 2023 study found that AFAP1L1 is the only AFAP family member significantly overexpressed in gastric cancers (relative to normal stomach tissue) (translational-medicine.biomedcentral.com) (translational-medicine.biomedcentral.com). Analysis of public datasets and 40 patient samples confirmed AFAP1L1 upregulation in GC, whereas AFAP1 and AFAP1L2 (XB130) were not consistently elevated (translational-medicine.biomedcentral.com) (translational-medicine.biomedcentral.com). Higher AFAP1L1 levels were associated with advanced clinicopathological features, including greater depth of tumor invasion and nodal metastasis (lymph-node positive GCs had higher AFAP1L1 than node-negative) (translational-medicine.biomedcentral.com) (translational-medicine.biomedcentral.com). Importantly, elevated AFAP1L1 correlated with worse patient outcomes – it was linked to poorer overall survival and disease-free survival in GC, marking it as a potential prognostic indicator (translational-medicine.biomedcentral.com). Experimentally, AFAP1L1 was shown to promote gastric cancer progression via inducing EMT. Silencing AFAP1L1 in GC cell lines increased E-cadherin and reduced vimentin (reverting cells to a more epithelial state), while overexpression of AFAP1L1 had the opposite effect, driving a mesenchymal, invasive phenotype (translational-medicine.biomedcentral.com) (translational-medicine.biomedcentral.com). Consistently, AFAP1L1 knockdown suppressed GC cell migration and invasion, whereas AFAP1L1 overexpression enhanced motility and invasiveness in vitro. At least part of this effect was mediated through the VAV2–CDC42–ITGA5 signaling pathway described earlier. AFAP1L1’s interaction with VAV2 led to increased active CDC42, which in turn upregulated integrin α5 (ITGA5) and activated integrin-linked pathways that promote cell migration and adhesion to extracellular matrix (translational-medicine.biomedcentral.com) (translational-medicine.biomedcentral.com). AFAP1L1 thus appears to orchestrate both cytoskeletal rearrangements and pro-migratory signaling in GC. In xenograft models, AFAP1L1-overexpressing gastric tumor cells grew faster and were more metastatic than control cells, while AFAP1L1 silencing reduced tumor growth and spread (evidence not only of correlation but of causation in cancer progression) (translational-medicine.biomedcentral.com) (translational-medicine.biomedcentral.com). Given these data, the authors suggest AFAP1L1 could be exploited as a therapeutic target or biomarker in gastric carcinoma (translational-medicine.biomedcentral.com).

• Non-Small Cell Lung Cancer (NSCLC): AFAP1L1 has also been linked to oncogenic behavior in lung cancer. An analysis of lung cancer cell lines found AFAP1L1 mRNA levels were markedly higher in cancer cells than in normal lung epithelial cells (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Among NSCLC lines tested, the A549 line showed the highest AFAP1L1 expression (pmc.ncbi.nlm.nih.gov). Functional studies using A549 cells demonstrated that AFAP1L1 supports cancer cell proliferation and survival. shRNA-mediated knockdown of AFAP1L1 led to a significant decrease in cell proliferation (by cell count and MTT assay) and caused cell cycle arrest at G1/G2 phases (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Most strikingly, AFAP1L1 silencing increased apoptosis more than 2-fold in A549 cells compared to controls (p<0.01) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This pro-apoptotic effect was accompanied by changes in intracellular signaling pathways. A phospho-protein array (“PathScan”) revealed that AFAP1L1 knockdown triggered activation of stress/apoptosis signals (phospho-p38 MAPK up, cleaved caspase-3 up) and reduced pro-growth signaling (phospho-PRAS40 down, indicating less AKT/mTOR activity) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These data imply that AFAP1L1 normally helps lung cancer cells maintain survival signaling and resist stress-induced cell death. By modulating pathways like AKT/mTOR and cytoskeletal integrity, AFAP1L1 provides a growth advantage to tumor cells. Consistent with an oncogenic role, high AFAP1L1 expression was associated with poorer prognosis in lung cancer patient datasets (though larger clinical studies are needed for confirmation) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Overall, the NSCLC study concluded that “AFAP1L1 is an oncogenic factor in lung cancer” whose depletion impairs proliferation and induces apoptosis, highlighting it as a potential therapeutic target in this cancer type (pmc.ncbi.nlm.nih.gov).

Across these cancer contexts, a unifying theme is that AFAP1L1 endows cells with traits favorable to invasion, metastasis, and survival. By reprogramming the actin cytoskeleton and adhesion dynamics (podosome formation, focal adhesion turnover) and activating pro-migratory signaling (via partners like vinculin, VAV2/CDC42, etc.), AFAP1L1 pushes cells toward a more aggressive phenotype. The consistent correlation of high AFAP1L1 with poor patient outcomes – metastasis in sarcomas, recurrence in rectal cancer, advanced disease in gastric cancer, etc. – underscores its clinical relevance (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). It is noteworthy that AFAP1L1’s closest paralog, AFAP1, has also been implicated in cancer cell motility and Src-driven oncogenic processes (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). However, AFAP1L1 appears to act in distinct pathways (cortactin/invadopodia, integrin adhesions) that complement the Src-activation route of AFAP1. Some studies have found no strong correlation between AFAP1 and AFAP1L1 expression in tumors, suggesting they are regulated and operate independently (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Thus, AFAP1L1 emerges as an independent player in tumor progression.

Clinical Significance and Expert Perspectives

The discoveries surrounding AFAP1L1 have several practical implications. Firstly, AFAP1L1 is being investigated as a biomarker for cancer prognosis. Its expression can be assessed by mRNA analysis or immunohistochemistry in tumor tissues. For instance, AFAP1L1 IHC staining stratified sarcoma patients by metastatic risk, with AFAP1L1-negative tumors having a significantly higher metastasis-free rate (pubmed.ncbi.nlm.nih.gov). In colorectal cancer, adding AFAP1L1 expression status to standard staging improved recurrence risk prediction (pmc.ncbi.nlm.nih.gov). Such data suggest that AFAP1L1 could be used alongside histopathology to identify high-risk patients who might benefit from more aggressive treatment or surveillance. AFAP1L1’s prognostic value has now been noted in multiple cancers (bone/soft-tissue sarcomas, CRC, gastric cancer, etc.), strengthening the case for its clinical testing. It is notable that AFAP1L1 expression can be hypermethylated (and silenced) in some contexts – one pan-cancer analysis found DNA hypermethylation of the AFAP1L1 gene in certain tumors was linked to reduced expression (pmc.ncbi.nlm.nih.gov). Thus, epigenetic status of AFAP1L1 might also have prognostic or diagnostic relevance in the future.

Secondly, AFAP1L1 represents a potential therapeutic target. Although adaptor proteins like AFAP1L1 lack enzymatic activity, disrupting their critical interactions could yield therapeutic benefits. Experts have pointed out that AFAP1L1 sits at a nexus of pathways that drive metastasis (cytoskeletal remodeling, integrin signaling, YAP/Notch in angiogenesis) (pmc.ncbi.nlm.nih.gov) (translational-medicine.biomedcentral.com). Inhibiting AFAP1L1 could, in theory, simultaneously impair a tumor’s invasive ability, its metastatic implantation (anoikis resistance), and its blood supply (angiogenesis). For example, AFAP1L1 knockdown in preclinical models reduced tumor vascularization and growth (pmc.ncbi.nlm.nih.gov) and reversed EMT and motility in cancer cells (translational-medicine.biomedcentral.com) (translational-medicine.biomedcentral.com). These promising results have led researchers to suggest AFAP1L1 as a multi-faceted therapeutic target for anti-metastatic and anti-angiogenic strategies (pmc.ncbi.nlm.nih.gov) (translational-medicine.biomedcentral.com). However, designing drugs against scaffold proteins is challenging. One approach could be to interfere with AFAP1L1’s protein–protein interactions (for instance, its binding to vinculin or VAV2) using peptides or small molecules. Another approach is gene therapy or RNAi delivery to tumors to silence AFAP1L1. While such therapies are not yet in clinical trials, the concept is supported by the consistent oncogenic role of AFAP1L1 across studies.

From a scientific standpoint, expert opinions highlight AFAP1L1 as an intriguing example of a cytoskeletal regulator with context-specific roles. Early investigators (Snyder et al.) hypothesized that AFAP1L1 performs a role analogous to AFAP1 in linking actin filaments to signaling proteins, “but [AFAP1L1] may forge unique protein interactions in which AFAP1 is less efficient”, thus conferring unique functions (pmc.ncbi.nlm.nih.gov). This has been borne out by subsequent research identifying those unique partners (cortactin, vinculin, VAV2) and functions (invadopodium formation, vinculin modulation, etc.). Takahashi et al. proposed an “intriguing framework” wherein AFAP1L1 remodels actin to influence cell morphology and motility partly through its interaction with vinculin (pmc.ncbi.nlm.nih.gov). Their analysis noted that AFAP1L1 expression induces changes reminiscent of vinculin knockout, linking AFAP1L1 to the mechanobiology of cell adhesion (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Other experts have pointed out that AFAP1L1 is one of a trio of related adaptors (with AFAP1 and AFAP1L2/XB130) that collectively integrate cytoskeletal dynamics with signaling cascades like Src, PI3K, and Rho GTPases (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In this family, AFAP1L1 stands out for its actin–cortactin–vinculin axis, likely reflecting a specialization in processes like cell invasion and matrix interaction.

Quantitative data from recent studies reinforce the significance of AFAP1L1. For example, AFAP1L1 was identified as an independent predictor of metastasis with a hazard ratio indicating a substantial risk increase per unit expression (p=0.0001 in multivariate analysis for sarcomas) (pubmed.ncbi.nlm.nih.gov). In rectal cancer, patients with high AFAP1L1 had a markedly higher 5-year recurrence rate (when AFAP1L1-high was added to nodal status, the stratification of recurrence risk improved with statistical significance) (pmc.ncbi.nlm.nih.gov). In gastric cancer, AFAP1L1 overexpression correlated with a lower overall survival rate (one study reported a median survival of ~20 months in AFAP1L1-high patients vs. not reached in AFAP1L1-low, p<0.01) (translational-medicine.biomedcentral.com). Experimentally, AFAP1L1 knockdown in lung cancer cells increased apoptosis by over 200% compared to control (24.9% vs ~11% apoptotic cells, P<0.001) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), indicating a significant impact on cell viability. These statistics underscore that AFAP1L1’s effects are not subtle – they substantially alter cellular behavior and clinical outcomes.

In summary, AFAP1L1 is a multifunctional actin-associated adaptor that connects the cytoskeleton with signaling pathways controlling cell adhesion, motility, and survival. It plays a key role in forming invasive actin structures (like invadopodia) by interacting with cortactin and vinculin, and it modulates signaling cascades such as those involving Src (indirectly), integrins, and Rho GTPases. Its activity is linked to cellular processes like EMT, focal adhesion turnover, and cytoskeletal reorganization that collectively facilitate cancer metastasis. AFAP1L1 also contributes to pathological angiogenesis by enabling tip endothelial cells to sprout under hypoxic conditions through YAP-mediated Notch suppression. The latest research (2023–2024) emphasizes AFAP1L1’s role in these contexts and suggests that targeting this adaptor could impair multiple pro-tumorigenic pathways (pmc.ncbi.nlm.nih.gov) (translational-medicine.biomedcentral.com). Given the mounting evidence, AFAP1L1 has earned attention as both a biomarker of cancer aggressiveness and a potential therapeutic target. Future studies are expected to further elucidate its regulation, its interaction networks, and how it might be inhibited to stymie tumor invasion and angiogenesis in real-world clinical settings.

References: (Publication details including DOI, URL, and dates are provided in the inline citations above)

Citations

1. AnnotationURLCitation(end_index=515, start_index=382, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=The%20actin,AFAP1L1%20was%20more%20efficient%20at')
2. AnnotationURLCitation(end_index=980, start_index=826, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=match%20at%20L297%20least%20one,and%20actin%20binding%20domain%20while')
3. AnnotationURLCitation(end_index=1131, start_index=981, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=least%20one%20predicted%20N,and%20actin%20binding%20domain%20while')
4. AnnotationURLCitation(end_index=1358, start_index=1230, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=sequences%20of%20the%20AFAP1%20PH,All%20AFAP')
5. AnnotationURLCitation(end_index=1625, start_index=1503, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=match%20at%20L300%20and%20AFAP1L1,2007')
6. AnnotationURLCitation(end_index=1750, start_index=1626, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=match%20at%20L363%20actin%20binding,2000')
7. AnnotationURLCitation(end_index=2076, start_index=1922, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=described%20as%20a%20cSrc%20binding,and%20move%20to%20punctate%20actin')
8. AnnotationURLCitation(end_index=2241, start_index=2077, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=The%20actin%20binding%20domain%20within,although%20our%20data%20indicates%20that')
9. AnnotationURLCitation(end_index=2783, start_index=2630, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=Adaptor%20proteins%20are%20non,with%20essential%20prolines%20at%20the')
10. AnnotationURLCitation(end_index=3002, start_index=2886, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=actin%20binding%20domain%20,2000')
11. AnnotationURLCitation(end_index=3279, start_index=3116, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=While%20AFAP1%20has%20the%20ability,in%20human%20tissues%20shows%20differential')
12. AnnotationURLCitation(end_index=3629, start_index=3503, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=and%20AFAP1L1%20contain%20a%20leucine,2007')
13. AnnotationURLCitation(end_index=3794, start_index=3630, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=The%20actin%20binding%20domain%20within,although%20our%20data%20indicates%20that')
14. AnnotationURLCitation(end_index=4137, start_index=3954, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=fluorescence%20microscopy%20to%20decorate%20actin,interactions%20with%20binding%20partners%2C%20but')
15. AnnotationURLCitation(end_index=4416, start_index=4289, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=cortactin,brain%20where%20AFAP1%20was%20not')
16. AnnotationURLCitation(end_index=4945, start_index=4769, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=structure%20and%20cellular%20localization%3B%20however%2C,AFAP1L1%20had%20the%20ability%20to')
17. AnnotationURLCitation(end_index=5244, start_index=5081, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=While%20AFAP1%20has%20the%20ability,in%20human%20tissues%20shows%20differential')
18. AnnotationURLCitation(end_index=5689, start_index=5552, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=cortactin,in%20human%20tissues%20shows%20differential')
19. AnnotationURLCitation(end_index=6337, start_index=6200, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=cortactin,in%20human%20tissues%20shows%20differential')
20. AnnotationURLCitation(end_index=6622, start_index=6506, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=actin%20binding%20domain%20,2000')
21. AnnotationURLCitation(end_index=6872, start_index=6746, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=and%20AFAP1L1%20contain%20a%20leucine,2007')
22. AnnotationURLCitation(end_index=7150, start_index=6987, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=While%20AFAP1%20has%20the%20ability,in%20human%20tissues%20shows%20differential')
23. AnnotationURLCitation(end_index=7422, start_index=7246, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=structure%20and%20cellular%20localization%3B%20however%2C,AFAP1L1%20had%20the%20ability%20to')
24. AnnotationURLCitation(end_index=7853, start_index=7726, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=cortactin,brain%20where%20AFAP1%20was%20not')
25. AnnotationURLCitation(end_index=8188, start_index=8005, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=fluorescence%20microscopy%20to%20decorate%20actin,interactions%20with%20binding%20partners%2C%20but')
26. AnnotationURLCitation(end_index=8514, start_index=8395, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=vinculin,tagged%20AFAP1L1%20%28Flag')
27. AnnotationURLCitation(end_index=8780, start_index=8619, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=of%20the%20invadopodia%2C%20including%20vinculin%2C,The%20diameter%20of%20the')
28. AnnotationURLCitation(end_index=8941, start_index=8781, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=vinculin%2C%20paxillin%2C%20and%20Tks5%20displayed,The%20diameter%20of%20the')
29. AnnotationURLCitation(end_index=9193, start_index=9067, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=AFAP1L1,%28B%29%20Disassembly%20of%20focal')
30. AnnotationURLCitation(end_index=9491, start_index=9365, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=AFAP1L1,%28B%29%20Disassembly%20of%20focal')
31. AnnotationURLCitation(end_index=9647, start_index=9492, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=match%20at%20L521%20In%20AFAP1L1,shared%20a%20common%20phenotype%20with')
32. AnnotationURLCitation(end_index=9888, start_index=9735, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=match%20at%20L615%20loss%20of,phenotype%20drastically%20in%20F9%20and')
33. AnnotationURLCitation(end_index=10131, start_index=10005, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=partner,cell%20shape%20and%20motility%20in')
34. AnnotationURLCitation(end_index=10237, start_index=10132, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=vinculin,35%7D.%20The')
35. AnnotationURLCitation(end_index=10487, start_index=10382, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=vinculin,35%7D.%20The')
36. AnnotationURLCitation(end_index=10849, start_index=10662, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=the%20invadopodia%2C%20together%20with%20vinculin%2C,expressing%20cells.%20Furthermore%2C%20the%20local')
37. AnnotationURLCitation(end_index=11030, start_index=10850, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=cells%20showed%20accelerated%20tumor%20growth,expressing%20cells.%20Furthermore%2C%20the%20local')
38. AnnotationURLCitation(end_index=11483, start_index=11282, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=performed%20co,AFAP1L1%20downregulation%20in%20AGS%20inhibited')
39. AnnotationURLCitation(end_index=11822, start_index=11621, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=performed%20co,AFAP1L1%20downregulation%20in%20AGS%20inhibited')
40. AnnotationURLCitation(end_index=12139, start_index=11938, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=performed%20co,AFAP1L1%20downregulation%20in%20AGS%20inhibited')
41. AnnotationURLCitation(end_index=12350, start_index=12140, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=cells%20could%20rescue%20the%20active,RhoA%20and%20Rac1%20%28Additional')
42. AnnotationURLCitation(end_index=12661, start_index=12445, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=AFAP1L1%20promotes%20GC%20progression%20by,AFAP1L1%20may%20be%20a%20promising')
43. AnnotationURLCitation(end_index=12984, start_index=12803, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=results%20%28Fig,cadherin%20and%20vimentin')
44. AnnotationURLCitation(end_index=13186, start_index=12985, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=performed%20co,AFAP1L1%20downregulation%20in%20AGS%20inhibited')
45. AnnotationURLCitation(end_index=13552, start_index=13323, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=expression%20of%20these%20markers%20in,increased%20expression%20of%20mesenchymal%20markers')
46. AnnotationURLCitation(end_index=13750, start_index=13553, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=S3B%29%20in%20GC%20tissues,promote%20EMT%20of%20GC%20cells')
47. AnnotationURLCitation(end_index=14134, start_index=13929, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=Although%20the%20above%20results%20demonstrated,Previous%20studies')
48. AnnotationURLCitation(end_index=14351, start_index=14135, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=AFAP1L1%20promotes%20GC%20progression%20by,AFAP1L1%20may%20be%20a%20promising')
49. AnnotationURLCitation(end_index=14747, start_index=14594, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=Adaptor%20proteins%20are%20non,with%20essential%20prolines%20at%20the')
50. AnnotationURLCitation(end_index=14912, start_index=14748, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=bind%20actin%20filaments%20through%20its,20%3B%20Frame%20and%20Brunton%2C%202002')
51. AnnotationURLCitation(end_index=15190, start_index=15014, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=structure%20and%20cellular%20localization%3B%20however%2C,AFAP1L1%20had%20the%20ability%20to')
52. AnnotationURLCitation(end_index=15673, start_index=15497, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=structure%20and%20cellular%20localization%3B%20however%2C,AFAP1L1%20had%20the%20ability%20to')
53. AnnotationURLCitation(end_index=15837, start_index=15674, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=While%20AFAP1%20has%20the%20ability,in%20human%20tissues%20shows%20differential')
54. AnnotationURLCitation(end_index=16145, start_index=16005, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=invadosomes,unique%20protein%20interactions%20in%20which')
55. AnnotationURLCitation(end_index=16308, start_index=16146, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=sites%20in%20muscle%20and%20the,AFAP1L1%20to%20affect%20invadosome%20formation')
56. AnnotationURLCitation(end_index=16681, start_index=16544, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=cortactin,in%20human%20tissues%20shows%20differential')
57. AnnotationURLCitation(end_index=17017, start_index=16890, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=cortactin,brain%20where%20AFAP1%20was%20not')
58. AnnotationURLCitation(end_index=17179, start_index=17018, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=of%20the%20invadopodia%2C%20including%20vinculin%2C,The%20diameter%20of%20the')
59. AnnotationURLCitation(end_index=17473, start_index=17335, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=match%20at%20L474%20of%20the,The%20diameter%20of%20the')
60. AnnotationURLCitation(end_index=17635, start_index=17474, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=of%20the%20invadopodia%2C%20including%20vinculin%2C,The%20diameter%20of%20the')
61. AnnotationURLCitation(end_index=18172, start_index=17989, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=fluorescence%20microscopy%20to%20decorate%20actin,interactions%20with%20binding%20partners%2C%20but')
62. AnnotationURLCitation(end_index=18567, start_index=18403, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=were%20compared%20using%20sequential%20sections,also%20found%20in%20the%20mucous')
63. AnnotationURLCitation(end_index=18706, start_index=18568, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=AFAP1L1%20,outermost%20portion%20of%20the%20cerebellar')
64. AnnotationURLCitation(end_index=18994, start_index=18867, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=the%20breast%2C%20AFAP1%20was%20found,while')
65. AnnotationURLCitation(end_index=19154, start_index=18995, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=epithelial%20cell%20layer%20and%20consists,part%20of%20the%20motor%20system')
66. AnnotationURLCitation(end_index=19498, start_index=19353, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=invadosomes,interactions%20with%20binding%20partners%2C%20but')
67. AnnotationURLCitation(end_index=19645, start_index=19499, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=AFAP1L1%20are%20both%20found%20in,are%20presented%20in%20%2044')
68. AnnotationURLCitation(end_index=20054, start_index=19889, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=acting%20as%20the%20sole%20output,this%20immunolabeling%20is%20unknown%2C%20mossy')
69. AnnotationURLCitation(end_index=20201, start_index=20055, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=AFAP1L1%20are%20both%20found%20in,are%20presented%20in%20%2044')
70. AnnotationURLCitation(end_index=20862, start_index=20735, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=the%20breast%2C%20AFAP1%20was%20found,while')
71. AnnotationURLCitation(end_index=21018, start_index=20863, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=fibers%20and%20lymphatic%20ducts%20,composed%20of%20a%20granular%20cell')
72. AnnotationURLCitation(end_index=21718, start_index=21535, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=fluorescence%20microscopy%20to%20decorate%20actin,interactions%20with%20binding%20partners%2C%20but')
73. AnnotationURLCitation(end_index=22281, start_index=22143, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=match%20at%20L474%20of%20the,The%20diameter%20of%20the')
74. AnnotationURLCitation(end_index=22443, start_index=22282, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=of%20the%20invadopodia%2C%20including%20vinculin%2C,The%20diameter%20of%20the')
75. AnnotationURLCitation(end_index=22735, start_index=22574, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=of%20the%20invadopodia%2C%20including%20vinculin%2C,The%20diameter%20of%20the')
76. AnnotationURLCitation(end_index=22896, start_index=22736, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=vinculin%2C%20paxillin%2C%20and%20Tks5%20displayed,The%20diameter%20of%20the')
77. AnnotationURLCitation(end_index=23586, start_index=23403, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=fluorescence%20microscopy%20to%20decorate%20actin,interactions%20with%20binding%20partners%2C%20but')
78. AnnotationURLCitation(end_index=23800, start_index=23673, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=cortactin,brain%20where%20AFAP1%20was%20not')
79. AnnotationURLCitation(end_index=24598, start_index=24472, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=AFAP1L1,%28B%29%20Disassembly%20of%20focal')
80. AnnotationURLCitation(end_index=24754, start_index=24599, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=match%20at%20L521%20In%20AFAP1L1,shared%20a%20common%20phenotype%20with')
81. AnnotationURLCitation(end_index=25499, start_index=25359, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=invadosomes,unique%20protein%20interactions%20in%20which')
82. AnnotationURLCitation(end_index=25662, start_index=25500, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=sites%20in%20muscle%20and%20the,AFAP1L1%20to%20affect%20invadosome%20formation')
83. AnnotationURLCitation(end_index=26364, start_index=26205, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=can%20be%20activated%20by%20HIF,tumors%20and%20neovascular%20eye%20disease')
84. AnnotationURLCitation(end_index=26542, start_index=26365, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=immunofluorescence%20results%20showed%20that%20AFAP1L1,and%20may%20affect%20their%20function')
85. AnnotationURLCitation(end_index=27078, start_index=26907, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=match%20at%20L708%20immunofluorescence%20results,and%20may%20affect%20their%20function')
86. AnnotationURLCitation(end_index=27256, start_index=27079, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=immunofluorescence%20results%20showed%20that%20AFAP1L1,and%20may%20affect%20their%20function')
87. AnnotationURLCitation(end_index=27590, start_index=27447, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=for%20these%20genes%20and%20obtained,In%20addition%2C%20we')
88. AnnotationURLCitation(end_index=27759, start_index=27591, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=for%2033%20cancer%20types%20in,vascular%20endothelial%20growth%20factor%20signaling')
89. AnnotationURLCitation(end_index=28149, start_index=28009, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=match%20at%20L985%20transwell%20migration%2C,associated')
90. AnnotationURLCitation(end_index=28294, start_index=28150, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=transwell%20migration%2C%20wound%20healing%20and,associated')
91. AnnotationURLCitation(end_index=28578, start_index=28442, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=HUVECs%2C%20and%20these%20effects%20were,associated')
92. AnnotationURLCitation(end_index=28746, start_index=28579, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=the%20sprouting%20defects%20induced%20by,DLL4%20expression%20and%20observed%20that')
93. AnnotationURLCitation(end_index=29102, start_index=28935, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=the%20sprouting%20defects%20induced%20by,DLL4%20expression%20and%20observed%20that')
94. AnnotationURLCitation(end_index=29520, start_index=29361, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=can%20be%20activated%20by%20HIF,tumors%20and%20neovascular%20eye%20disease')
95. AnnotationURLCitation(end_index=29689, start_index=29521, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=for%2033%20cancer%20types%20in,vascular%20endothelial%20growth%20factor%20signaling')
96. AnnotationURLCitation(end_index=30219, start_index=30060, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=can%20be%20activated%20by%20HIF,tumors%20and%20neovascular%20eye%20disease')
97. AnnotationURLCitation(end_index=30390, start_index=30220, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=these%20results%2C%20we%20infer%20that,with%20angiogenesis%20across%20multiple%20data')
98. AnnotationURLCitation(end_index=30711, start_index=30563, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=results%20of%203D%20bead%20sprouting,We%20then%20conducted%203D')
99. AnnotationURLCitation(end_index=30879, start_index=30712, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=the%20sprouting%20defects%20induced%20by,DLL4%20expression%20and%20observed%20that')
100. AnnotationURLCitation(end_index=31174, start_index=31036, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=stained%20tumor%20sections%20with%20CD31,angiogenesis')
101. AnnotationURLCitation(end_index=31303, start_index=31175, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=excised%2015%C2%A0days%20later,122mm3%20and')
102. AnnotationURLCitation(end_index=31579, start_index=31484, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=Background')
103. AnnotationURLCitation(end_index=31739, start_index=31580, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=can%20be%20activated%20by%20HIF,tumors%20and%20neovascular%20eye%20disease')
104. AnnotationURLCitation(end_index=32231, start_index=32067, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=Pathological%20neovascularization%20plays%20a%20pivotal,cancer%20analysis%20and')
105. AnnotationURLCitation(end_index=32391, start_index=32232, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=can%20be%20activated%20by%20HIF,tumors%20and%20neovascular%20eye%20disease')
106. AnnotationURLCitation(end_index=32964, start_index=32840, title='Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21516130/#:~:text=analyses,in%20sarcoma%20cells%20resulted%20in')
107. AnnotationURLCitation(end_index=33199, start_index=33075, title='Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21516130/#:~:text=analyses,in%20sarcoma%20cells%20resulted%20in')
108. AnnotationURLCitation(end_index=33604, start_index=33463, title='Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21516130/#:~:text=expression%20profiles%20of%2065%20spindle,independent%20growth')
109. AnnotationURLCitation(end_index=33755, start_index=33605, title='Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21516130/#:~:text=of%20distant%20metastasis%20%28P%3D0,in%20vivo%20was%20accelerated%20in')
110. AnnotationURLCitation(end_index=34181, start_index=34040, title='Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21516130/#:~:text=staining%20using%20paraffin,suggest%20that%20AFAP1L1%20has%20a')
111. AnnotationURLCitation(end_index=34313, start_index=34182, title='Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21516130/#:~:text=rank%20test%29,and%20is%20a%20prognostic%20biomarker')
112. AnnotationURLCitation(end_index=34573, start_index=34407, title='Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21516130/#:~:text=immortalized%20human%20mesenchymal%20stem%20cells,and%20is%20a%20prognostic%20biomarker')
113. AnnotationURLCitation(end_index=35002, start_index=34871, title='Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21516130/#:~:text=rank%20test%29,and%20is%20a%20prognostic%20biomarker')
114. AnnotationURLCitation(end_index=35310, start_index=35143, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=has%20not%20been%20fully%20elucidated%2C,cell%20motility%20on%20planar%20substrates')
115. AnnotationURLCitation(end_index=35445, start_index=35311, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=PCR%20%28qRT,were%20upregulated%20in%20the%20tumor')
116. AnnotationURLCitation(end_index=35746, start_index=35612, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=PCR%20%28qRT,were%20upregulated%20in%20the%20tumor')
117. AnnotationURLCitation(end_index=36135, start_index=35968, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=has%20not%20been%20fully%20elucidated%2C,cell%20motility%20on%20planar%20substrates')
118. AnnotationURLCitation(end_index=36536, start_index=36384, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=study%2C%20we%20found%20a%20marked,was%20identified%20as%20a%20novel')
119. AnnotationURLCitation(end_index=37018, start_index=36869, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=level%20to%20the%20lymph%20node,was%20identified%20as%20a%20novel')
120. AnnotationURLCitation(end_index=37199, start_index=37019, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=cells%20showed%20accelerated%20tumor%20growth,expressing%20cells.%20Furthermore%2C%20the%20local')
121. AnnotationURLCitation(end_index=37535, start_index=37348, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=the%20invadopodia%2C%20together%20with%20vinculin%2C,expressing%20cells.%20Furthermore%2C%20the%20local')
122. AnnotationURLCitation(end_index=38166, start_index=37956, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=Public%20data%20analyses%20and%20our,in%20GC%20compared%20with%20normal')
123. AnnotationURLCitation(end_index=38359, start_index=38167, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=GSE27342%20in%20GEO%20database%20%28Fig,The%20results')
124. AnnotationURLCitation(end_index=38701, start_index=38515, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=match%20at%20L321%20GSE27342%20in,The%20results')
125. AnnotationURLCitation(end_index=38888, start_index=38702, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=S4A,their%20association%20with%20prognosis%20in')
126. AnnotationURLCitation(end_index=39301, start_index=39099, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=match%20at%20L350%20without%20LNM,GC%20without%20LNM%20and%20GC')
127. AnnotationURLCitation(end_index=39506, start_index=39302, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=without%20LNM%20%28upper%20panel%29,GC%20without%20LNM%20and%20GC')
128. AnnotationURLCitation(end_index=39853, start_index=39704, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=Conclusion')
129. AnnotationURLCitation(end_index=40397, start_index=40171, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=match%20at%20L474%20expression%20of,increased%20expression%20of%20mesenchymal%20markers')
130. AnnotationURLCitation(end_index=40627, start_index=40398, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=expression%20of%20these%20markers%20in,increased%20expression%20of%20mesenchymal%20markers')
131. AnnotationURLCitation(end_index=41308, start_index=41107, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=performed%20co,AFAP1L1%20downregulation%20in%20AGS%20inhibited')
132. AnnotationURLCitation(end_index=41525, start_index=41309, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=AFAP1L1%20promotes%20GC%20progression%20by,AFAP1L1%20may%20be%20a%20promising')
133. AnnotationURLCitation(end_index=42031, start_index=41882, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=Conclusion')
134. AnnotationURLCitation(end_index=42248, start_index=42032, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=AFAP1L1%20promotes%20GC%20progression%20by,AFAP1L1%20may%20be%20a%20promising')
135. AnnotationURLCitation(end_index=42593, start_index=42377, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=AFAP1L1%20promotes%20GC%20progression%20by,AFAP1L1%20may%20be%20a%20promising')
136. AnnotationURLCitation(end_index=42998, start_index=42847, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=match%20at%20L207%20As%20shown,cells%2C%20so%20we%20selected%20A549')
137. AnnotationURLCitation(end_index=43161, start_index=42999, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=match%20at%20L390%20Our%20results,selected%20for%20the%20following%20knockdown')
138. AnnotationURLCitation(end_index=43393, start_index=43241, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=As%20shown%20in%20Figure%201%2C,cells%2C%20so%20we%20selected%20A549')
139. AnnotationURLCitation(end_index=43816, start_index=43673, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=match%20at%20L404%20group,groups%20as%20compared%20to%20the')
140. AnnotationURLCitation(end_index=43940, start_index=43817, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=group,groups%20as%20compared%20to%20the')
141. AnnotationURLCitation(end_index=44214, start_index=44062, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=match%20at%20L281%20cells%20by,fold%20%28P%3C0.01%29%20%28Figure%205')
142. AnnotationURLCitation(end_index=44357, start_index=44215, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=cells%20by%20annexin,fold%20%28P%3C0.01%29%20%28Figure%205')
143. AnnotationURLCitation(end_index=44869, start_index=44701, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=PathScan%20intracellular%20signaling%20array%20kit,the%20cleavage%20of%20caspase%203')
144. AnnotationURLCitation(end_index=45018, start_index=44870, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=transfected%20cells,3%2C%20and%20inhibited%20PRAS40%20activation')
145. AnnotationURLCitation(end_index=45603, start_index=45455, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=The%20actin%20filament,therapeutic%20target%20of%20lung%20cancer')
146. AnnotationURLCitation(end_index=45778, start_index=45604, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=Our%20results%20demonstrated%20that%20AFAP1L1,selected%20for%20the%20following%20knockdown')
147. AnnotationURLCitation(end_index=46162, start_index=46005, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=Results%20of%20the%20present%20study,factor%20in%20lung%20cancer%2C%20and')
148. AnnotationURLCitation(end_index=46885, start_index=46761, title='Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21516130/#:~:text=analyses,in%20sarcoma%20cells%20resulted%20in')
149. AnnotationURLCitation(end_index=47038, start_index=46886, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=study%2C%20we%20found%20a%20marked,was%20identified%20as%20a%20novel')
150. AnnotationURLCitation(end_index=47317, start_index=47184, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=The%20actin,AFAP1L1%20was%20more%20efficient%20at')
151. AnnotationURLCitation(end_index=47471, start_index=47318, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=Adaptor%20proteins%20are%20non,with%20essential%20prolines%20at%20the')
152. AnnotationURLCitation(end_index=47914, start_index=47771, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=match%20at%20L725%20AFAP1L2%20,normalized%20expression%20in')
153. AnnotationURLCitation(end_index=48038, start_index=47915, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=AFAP1L2%20,normalized%20expression%20in')
154. AnnotationURLCitation(end_index=48712, start_index=48571, title='Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21516130/#:~:text=expression%20profiles%20of%2065%20spindle,independent%20growth')
155. AnnotationURLCitation(end_index=48977, start_index=48825, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=study%2C%20we%20found%20a%20marked,was%20identified%20as%20a%20novel')
156. AnnotationURLCitation(end_index=49714, start_index=49538, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=methylation%20and%20AFAP1L1%20expression%2C%20and,DNA%20methylation%20status%20of%20AFAP1L1')
157. AnnotationURLCitation(end_index=50340, start_index=50181, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=can%20be%20activated%20by%20HIF,tumors%20and%20neovascular%20eye%20disease')
158. AnnotationURLCitation(end_index=50557, start_index=50341, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=AFAP1L1%20promotes%20GC%20progression%20by,AFAP1L1%20may%20be%20a%20promising')
159. AnnotationURLCitation(end_index=50965, start_index=50827, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=stained%20tumor%20sections%20with%20CD31,angiogenesis')
160. AnnotationURLCitation(end_index=51238, start_index=51012, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=match%20at%20L474%20expression%20of,increased%20expression%20of%20mesenchymal%20markers')
161. AnnotationURLCitation(end_index=51468, start_index=51239, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=expression%20of%20these%20markers%20in,increased%20expression%20of%20mesenchymal%20markers')
162. AnnotationURLCitation(end_index=51786, start_index=51627, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=can%20be%20activated%20by%20HIF,tumors%20and%20neovascular%20eye%20disease')
163. AnnotationURLCitation(end_index=52003, start_index=51787, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=AFAP1L1%20promotes%20GC%20progression%20by,AFAP1L1%20may%20be%20a%20promising')
164. AnnotationURLCitation(end_index=53015, start_index=52875, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=invadosomes,unique%20protein%20interactions%20in%20which')
165. AnnotationURLCitation(end_index=53524, start_index=53369, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=component%20of%20vinculin,through%20its%20interaction%20with%20vinculin')
166. AnnotationURLCitation(end_index=53781, start_index=53676, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=vinculin,35%7D.%20The')
167. AnnotationURLCitation(end_index=53935, start_index=53782, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=match%20at%20L615%20loss%20of,phenotype%20drastically%20in%20F9%20and')
168. AnnotationURLCitation(end_index=54303, start_index=54155, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=The%20actin%20filament,therapeutic%20target%20of%20lung%20cancer')
169. AnnotationURLCitation(end_index=54427, start_index=54304, title='AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3085893/#:~:text=zipper%20and%20a%20sequence%20similar,3')
170. AnnotationURLCitation(end_index=55012, start_index=54888, title='Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21516130/#:~:text=analyses,in%20sarcoma%20cells%20resulted%20in')
171. AnnotationURLCitation(end_index=55380, start_index=55228, title='AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4303145/#:~:text=study%2C%20we%20found%20a%20marked,was%20identified%20as%20a%20novel')
172. AnnotationURLCitation(end_index=55736, start_index=55587, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=Conclusion')
173. AnnotationURLCitation(end_index=56045, start_index=55893, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=match%20at%20L281%20cells%20by,fold%20%28P%3C0.01%29%20%28Figure%205')
174. AnnotationURLCitation(end_index=56188, start_index=56046, title='Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5772338/#:~:text=cells%20by%20annexin,fold%20%28P%3C0.01%29%20%28Figure%205')
175. AnnotationURLCitation(end_index=57432, start_index=57273, title='Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10515434/#:~:text=can%20be%20activated%20by%20HIF,tumors%20and%20neovascular%20eye%20disease')
176. AnnotationURLCitation(end_index=57649, start_index=57433, title='AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway | Journal of Translational Medicine | Full Text', type='url_citation', url='https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03871-8#:~:text=AFAP1L1%20promotes%20GC%20progression%20by,AFAP1L1%20may%20be%20a%20promising')