Introduction & Gene Overview OpenAI o3-deep-research-2025-06-26 107 citations 2025-12-27T22:09:39.225044

Introduction & Gene Overview

VOPP1 (Vesicular, Overexpressed in Cancer, Prosurvival Protein 1) is a human gene encoding a small protein (172 amino acids) known for its role in cell survival and cancer biology (www.ncbi.nlm.nih.gov) (www.nature.com). It was initially identified in chromosome 7p11.2 within the EGFR amplification region frequently seen in glioblastoma, hence early names GASP (“glioblastoma-amplified secreted protein”) and ECOP (“EGFR-coamplified and overexpressed protein”) (www.nature.com). The official gene symbol VOPP1 reflects its characterization as a “WW domain-binding protein,” indicating it binds to proteins containing WW domains. Indeed, VOPP1 contains conserved proline-rich PPPY motifs that mediate binding to WW-domain proteins (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The protein is synthesized as a precursor with a signal peptide (“Flags: Precursor” in UniProt), targeting it to the secretory/endosomal pathway. Consistent with this, confocal microscopy has localized VOPP1 to intracellular vesicles (late endosomes/lysosomes) clustered near the nucleus (pubmed.ncbi.nlm.nih.gov). Bioinformatic and antibody-based profiling predict VOPP1 to be an intracellular membrane-associated protein, likely residing on vesicular/lysosomal membranes (www.proteinatlas.org) (pubmed.ncbi.nlm.nih.gov). VOPP1 is ubiquitously expressed at baseline in human tissues, with especially high mRNA levels in the retina and certain tumors (www.proteinatlas.org) (www.proteinatlas.org). Importantly, its expression is frequently elevated in cancers such as glioblastoma, squamous cell carcinomas, breast and gastric tumors (www.nature.com) (pubmed.ncbi.nlm.nih.gov), suggesting an oncogenic function. Below, we discuss the current understanding of VOPP1’s function, recent research (2023–2024), its roles in disease and potential clinical applications, expert insights, and key data from recent studies, with emphasis on authoritative sources.

Function and Mechanisms: NF-κB Activation and Survival

One of the key functions of VOPP1 is regulating the NF-κB signaling pathway to promote cell survival. NF-κB is a transcription factor controlling genes for inflammation and anti-apoptotic proteins. VOPP1 enhances canonical NF-κB activity: experimental overexpression of VOPP1 (ECOP) drives NF-κB p50/p65 to translocate into the nucleus and bind DNA, boosting NF-κB-dependent transcription (www.nature.com). This heightened NF-κB activity, in turn, confers resistance to apoptosis (programmed cell death) under stress conditions (www.nature.com). Conversely, silencing VOPP1 dampens NF-κB signaling – when VOPP1 is knocked down, cells show delayed degradation of IκBα (the inhibitor of NF-κB), leading to slower NF-κB nuclear entry and reduced target gene expression (www.nature.com). As a result, VOPP1-depleted cells become more susceptible to apoptotic triggers (www.nature.com). These findings (first reported in 2011) established VOPP1 as a positive regulator of NF-κB. Researchers described VOPP1 as a “key regulator” of NF-κB signaling whose overexpression (for example, via gene amplification with EGFR) could promote cell survival and therapy resistance by keeping NF-κB active (www.nature.com). Notably, this NF-κB enhancement by VOPP1 seems to operate via controlling IκBα turnover – suggesting VOPP1 might influence the ubiquitin-proteasome machinery or signaling upstream of IκB degradation, although the precise biochemical mechanism is still being clarified.

Beyond NF-κB, VOPP1 has been implicated in maintaining cellular redox balance and mitochondrial integrity, further supporting its pro-survival role. In cancer cells that naturally overexpress VOPP1, acute knockdown of VOPP1 triggers intrinsic apoptosis accompanied by oxidative stress (www.nature.com) (www.nature.com). For example, in squamous carcinoma cell lines (SCC) and HeLa cells, VOPP1 silencing caused cell death within ~72 hours via the intrinsic (mitochondrial) apoptotic pathway (www.nature.com). Gene expression profiling of these VOPP1-depleted cells showed enrichment of oxidative stress and mitochondrial dysfunction signatures (www.nature.com). Indeed, investigators observed a rise in reactive oxygen species (ROS) and loss of mitochondrial membrane potential following VOPP1 knockdown (www.nature.com). Strikingly, treating the cells with the antioxidant N-acetylcysteine could rescue them from apoptosis, indicating that excess ROS is a major driver of cell death when VOPP1 is lost (www.nature.com). This suggests VOPP1 normally helps limit oxidative damage, either by regulating antioxidant gene expression (potentially via NF-κB target genes) or by influencing organelle function. Interestingly, in those SCC cells, NF-κB reporter activity was not significantly changed by VOPP1 knockdown (www.nature.com), implying VOPP1’s redox protective function might be partially independent of NF-κB or context-dependent. Nonetheless, taken together, these findings indicate that VOPP1 is a multi-faceted prosurvival protein: it augments pro-survival signaling (NF-κB) and guards against oxidative stress-induced damage, thereby supporting the survival and proliferation of cells.

Localization and Interactions: Lysosomal Sequestration and WW Domain Binding

At the subcellular level, VOPP1 is a vesicle-associated protein. Immunofluorescence studies have shown that VOPP1 localizes predominantly to perinuclear endo/lysosomal compartments (pubmed.ncbi.nlm.nih.gov). In gastric cancer cells, for example, GFP-tagged VOPP1 was found concentrated on lysosomal membranes near the nucleus (pubmed.ncbi.nlm.nih.gov), consistent with earlier reports in other cell types. This localization aligns with VOPP1’s having a signal peptide and a predicted membrane association. Notably, VOPP1 lacks any well-known catalytic domains – instead, it functions through protein–protein interactions. As its name suggests, VOPP1 can bind “WW” domains (protein interaction modules that recognize proline-rich PPxY motifs). VOPP1 contains PPXY sequence motifs in its C-terminal region (pubmed.ncbi.nlm.nih.gov), and these motifs mediate binding to WW-domain proteins. A prime example is the tumor suppressor WWOX (WW domain-containing oxidoreductase). WWOX carries two N-terminal WW domains and is frequently lost or inactivated in cancers. Proteomic analyses (TAP–mass spectrometry) identified VOPP1 as a top WWOX-binding partner, interacting specifically via the PPPY motif of VOPP1 and the first WW domain of WWOX (pmc.ncbi.nlm.nih.gov). Co-immunoprecipitation confirmed a direct VOPP1–WWOX interaction in cells (pubmed.ncbi.nlm.nih.gov). Significantly, VOPP1–WWOX binding has functional consequences: VOPP1 can literally sequester WWOX inside lysosomal vesicles, away from its usual sites of action (bmcbiol.biomedcentral.com).

This WWOX sequestration mechanism was elucidated in a 2018 study focusing on breast cancer. Researchers discovered that VOPP1 acts as a negative regulator of WWOX’s tumor suppressor function (bmcbiol.biomedcentral.com). Under normal conditions, WWOX promotes apoptosis (for instance by binding pro-apoptotic transcription factor p73α). But in breast cancer cells that express high VOPP1, VOPP1 binds to WWOX and traps it in the lysosomal compartment, preventing WWOX from interacting with p73α and other partners (bmcbiol.biomedcentral.com). This interaction functionally “silences” WWOX, impairing WWOX-mediated apoptosis and tumor suppression (bmcbiol.biomedcentral.com). The outcome is that cancer cells can survive and proliferate despite having an intact WWOX gene. In line with this, VOPP1 overexpression was shown to enhance oncogenic phenotypes: experimentally increasing VOPP1 levels in breast epithelial cells led to increased cellular transformation in vitro and faster tumor growth in vivo (mouse xenografts) (bmcbiol.biomedcentral.com). Clinically, the study found that VOPP1 is overexpressed in many breast tumors, especially those that still retain wild-type WWOX (bmcbiol.biomedcentral.com). Moreover, high VOPP1 expression correlates with significantly worse patient survival in breast cancers that are WWOX-positive (but not in WWOX-negative cases that lack the target) (bmcbiol.biomedcentral.com). These data indicate that VOPP1 is an oncogenic factor at least in part by disabling WWOX – effectively mimicking a WWOX loss-of-function even when WWOX is present (bmcbiol.biomedcentral.com). This concept has been echoed by experts: a 2023 review highlighted VOPP1 as a “significant regulator of WWOX”, noting that overexpression of VOPP1 (through its PPPY motif binding WWOX’s WW domain) diminishes WWOX’s tumor-suppressive functions (pmc.ncbi.nlm.nih.gov). In summary, VOPP1’s ability to interact with specific WW-domain proteins (like WWOX) in vesicular compartments is central to its role in modulating signaling pathways and cell fate. By tethering crucial factors in endo-lysosomal sites, VOPP1 can alter the balance of pro- and anti-apoptotic signals inside the cell.

Roles in Cancer: Oncogenic Impact and Clinical Relevance

Given its pro-survival functions, it is not surprising that VOPP1 has emerged as a context-dependent oncogene. The gene is frequently overexpressed or amplified in various cancers, and experimental studies support its tumor-promoting activity. In glioblastoma multiforme (GBM), VOPP1 resides in the same 7p11.2 amplicon as EGFR – a region amplified in ~40% of GBMs. Co-amplification leads to VOPP1 overexpression alongside EGFR (www.nature.com). It has been proposed that high VOPP1 in EGFR-amplified tumors contributes to the aggressive behavior of these cancers by enhancing NF-κB–driven survival signals (www.nature.com). Indeed, The Cancer Genome Atlas data indicate VOPP1 mRNA is particularly elevated in GBM tumors compared to most other cancer types (www.proteinatlas.org). Beyond brain tumors, VOPP1 upregulation is observed in many epithelial cancers. For example, gastric adenocarcinoma tissues show elevated VOPP1 protein expression relative to adjacent normal stomach tissue (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). In one study, immunohistochemistry and Western blots confirmed overexpression of VOPP1 in gastric tumors (pubmed.ncbi.nlm.nih.gov). Functionally, manipulating VOPP1 levels in a gastric cancer cell line (AGS) impacted its malignancy: ectopic VOPP1 overexpression promoted cell proliferation and migration, while RNAi silencing of VOPP1 suppressed these traits (pubmed.ncbi.nlm.nih.gov). The same study visualized VOPP1’s subcellular localization in cancer cells, finding VOPP1 concentrated on lysosomal membranes in the perinuclear area, consistent with its proposed mode of action (pubmed.ncbi.nlm.nih.gov). Likewise, in squamous cell carcinomas, VOPP1 is often overexpressed; as discussed, acute loss of VOPP1 triggers apoptosis in SCC cells (www.nature.com), highlighting that these cancer cells become “addicted” to VOPP1 for survival. In breast cancer, as detailed above, VOPP1 overexpression correlates with poorer outcomes in patients with functional WWOX (bmcbiol.biomedcentral.com) and directly drives tumorigenic processes by neutralizing WWOX (bmcbiol.biomedcentral.com). There is also evidence that VOPP1 may be involved in hepatocellular carcinoma and other malignancies. The Human Protein Atlas identifies VOPP1 as an unfavorable prognostic marker in liver cancer: high VOPP1 expression in hepatocellular carcinoma is associated with significantly shorter patient survival (p < 0.001) (www.proteinatlas.org). This suggests VOPP1 could serve as a biomarker for aggressive disease in certain contexts. More broadly, numerous studies have found oncogenic non-coding RNAs targeting the VOPP1 pathway – for instance, loss of certain microRNAs (e.g. miR-218 or others) or gain of specific lncRNAs can lead to VOPP1 upregulation, driving cancer progression (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Such findings underscore VOPP1’s position in a network of oncogenic signals.

Importantly, VOPP1’s contribution to cancer appears to involve multiple pathways. Its original link to NF-κB activation suggests that VOPP1-overexpressing tumors may exhibit chronic NF-κB activity, supporting inflammation, cell survival, and therapy resistance. In fact, sustained NF-κB signaling is one mechanism by which VOPP1-overexpressing cancer cells evade apoptosis (www.nature.com). For example, a study in cervical cancer reported that knocking down a long noncoding RNA suppressed tumor growth by upregulating a microRNA that in turn downregulated VOPP1, thereby reducing NF-κB activity and cancer cell invasiveness (pmc.ncbi.nlm.nih.gov). Separately, the VOPP1–WWOX interaction axis adds another tumorigenic mechanism: by crippling WWOX, VOPP1 can unleash pro-tumor pathways that WWOX normally restrains (WWOX influences apoptosis, DNA damage response, and Wnt/TGF-β signaling (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)). Thus, VOPP1 acts as a “dual threat” oncogene – it amplifies pro-survival/inflammatory signaling and inactivates a major tumor suppressor. Recognizing these roles, researchers have proposed VOPP1 as a potential therapeutic target. In principle, inhibiting VOPP1 or its critical interactions could re-sensitize cancer cells to apoptosis. For example, silencing VOPP1 induced widespread cell death in multiple cancer cell models (www.nature.com), and suppressing VOPP1 greatly reduced tumor growth in xenograft experiments (bmcbiol.biomedcentral.com). While no VOPP1-targeted drugs exist yet, these proofs-of-concept highlight the appeal of targeting VOPP1 in tumors that are “addicted” to it for survival. Additionally, the co-amplification of VOPP1 with EGFR in GBM suggests that therapies aimed at EGFR-amplified tumors might consider VOPP1’s status, as it could modulate responses (for instance, high VOPP1 levels might confer resistance to EGFR inhibitors by activating NF-κB). In summary, ample evidence supports VOPP1 as a context-dependent oncogene, making it both a biomarker of aggressive disease and a candidate therapeutic target in cancers characterized by its overexpression.

Emerging Roles and Recent Developments (2023–2025)

While much attention has focused on cancer, recent research (2023–2025) has uncovered roles for VOPP1 in other diseases and novel genetic events involving VOPP1. Notably, in 2025 VOPP1 was identified as a novel susceptibility gene for Rheumatoid Arthritis (RA) (pmc.ncbi.nlm.nih.gov). RA is an autoimmune disease characterized by chronic joint inflammation and hyperplasia of synovial fibroblasts. Using integrated genomics and Mendelian randomization, Wu et al. (2025) found that genetic variants increasing VOPP1 expression are associated with higher RA risk (odds ratio ~1.11 per allele, p≈0.01) (pmc.ncbi.nlm.nih.gov). They further observed VOPP1 is significantly upregulated in RA patient tissues – RA synovial biopsies and cultured RA fibroblast-like synoviocytes (FLS) had much higher VOPP1 protein levels than non-RA controls (p<0.001) (pmc.ncbi.nlm.nih.gov). This suggests VOPP1 might contribute to the pathogenic activation of RA synovial cells. Functional experiments confirmed this: knocking down VOPP1 in RA-FLS attenuated inflammatory and proliferative features. In vitro, VOPP1 silencing in RA-FLS reduced the phosphorylation of p38 MAPK (a stress/inflammation kinase), and decreased the production of pro-inflammatory cytokines TNF-α and IL-6 (pmc.ncbi.nlm.nih.gov). Loss of VOPP1 also slowed RA-FLS proliferation and even induced more cell cycle arrest (pmc.ncbi.nlm.nih.gov). These effects could be partially reversed by chemically re-activating p38, indicating that VOPP1 promotes RA-FLS proliferation and cytokine release at least in part via the p38 MAPK pathway (pmc.ncbi.nlm.nih.gov). Strikingly, the same study tested VOPP1 inhibition in vivo: they administered VOPP1 siRNA treatment in a collagen-induced arthritis rat model. Rats treated with VOPP1 silencing showed significantly alleviated RA symptoms – with reduced paw swelling, less inflammatory cell infiltration, and lower clinical arthritis scores compared to controls (pmc.ncbi.nlm.nih.gov). These findings position VOPP1 as a driver of inflammatory joint disease, linking its cell-survival role to immune cell/fibroblast hyperactivation. It is an intriguing development that a gene first characterized in cancer may also be a therapeutic target in autoimmune disorders**. The RA study authors suggest VOPP1 influences RA by modulating a metabolic mediator (an unknown metabolite flagged by their analysis) and by enhancing inflammatory signaling in synovial cells (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). While further research is needed, this opens the door to repurposing VOPP1-focused interventions beyond oncology.

Another recent development is the discovery of a gene fusion involving VOPP1 in a brain tumor. In 2025, Braune et al. reported a unique VOPP1::EGFR fusion gene in a glioneuronal tumor (ganglioglioma) (pmc.ncbi.nlm.nih.gov). This fusion joined part of the VOPP1 gene (Exon 1) with EGFR (Exon 18) in-frame, creating a hybrid protein. The patient’s tumor showed evidence of NF-κB pathway activation, which the authors attributed to the VOPP1 portion of the fusion driving NF-κB signaling (pmc.ncbi.nlm.nih.gov). Gangliogliomas typically harbor MAPK pathway mutations (like BRAF V600E), so a fusion engaging NF-κB is novel. This case implies that when fused to EGFR, VOPP1’s NF-κB activation function might synergize with EGFR signaling, potentially contributing to tumorigenesis. While a single case, it expands the spectrum of VOPP1’s involvement in cancer genomics and underscores the protein’s ability to activate NF-κB in a pathological setting. It is also a reminder that VOPP1 lies in the vicinity of EGFR on chromosome 7, so structural genomic alterations in that region can simultaneously affect both genes. The finding of a VOPP1–EGFR fusion hints that future tumor sequencing efforts may uncover additional VOPP1-containing fusions or co-amplifications, especially in brain tumors. Clinically, if such fusions are present, they could be relevant for targeted therapies (for example, NF-κB or EGFR pathway inhibitors).

Finally, continued research into VOPP1’s molecular network is revealing more about its regulation. A 2024 review on WWOX noted that genes regulating WWOX (like VOPP1) may represent “oncogenic networks” that bypass direct tumor suppressor loss (pmc.ncbi.nlm.nih.gov). And additional interactors of VOPP1 are being explored: for instance, VOPP1 was found to interact with proteins involved in vesicle trafficking (e.g. SCAMP3, SEC23IP) as part of the WWOX interactome (pubmed.ncbi.nlm.nih.gov). These findings raise new questions: Does VOPP1 affect autophagy or lysosomal function? Are there other signaling pathways (besides NF-κB and p38) that it modulates? Ongoing studies in 2023–2024 are likely to shed more light on these aspects, as VOPP1 is now on the radar in fields beyond oncology (such as immunology and metabolism).

Clinical Significance and Applications

Understanding VOPP1’s function has practical implications in medicine. In oncology, VOPP1 is being evaluated as a biomarker and a potential therapeutic target. Its expression level in tumors often correlates with disease severity or outcome. For example, as noted, high VOPP1 predicts worse prognosis in liver cancer patients (www.proteinatlas.org) and in subsets of breast cancer patients (those with intact WWOX) (bmcbiol.biomedcentral.com). In gastric cancer, elevated VOPP1 in tumors (compared to normal tissue) has been observed, and by extrapolation it might serve as a diagnostic or prognostic marker (pubmed.ncbi.nlm.nih.gov). Some studies have suggested measuring VOPP1 or its regulators (like miR-218) as biomarkers for cancer progression (pubmed.ncbi.nlm.nih.gov). Moreover, since VOPP1 lies in the commonly amplified 7p11.2 region, its copy number could be assessed in tumors where EGFR amplification is found, to identify cases of co-amplification. In GBM and other tumors, detecting VOPP1 amplification or overexpression could inform clinicians about the tumor’s reliance on NF-κB survival pathways. There is also interest in VOPP1 as a drug target. Although VOPP1 is not an enzyme (so not directly “druggable” with small inhibitors in a classical sense), disrupting its critical interactions is a potential strategy. For instance, interfering with the VOPP1–WWOX binding (perhaps by mimicking the PPXY motif to compete for WWOX’s WW domain) could release WWOX to carry out its tumor suppressor function (pmc.ncbi.nlm.nih.gov). Similarly, blocking VOPP1’s effect on NF-κB signaling – for example by using NF-κB pathway inhibitors in tumors known to have high VOPP1 – might yield therapeutic benefit (essentially counteracting the ECOP/NF-κB axis). Some researchers have proposed that tumors with VOPP1 overexpression might be especially vulnerable to NF-κB inhibition or to pro-oxidant therapies, since those tumors are “addicted” to VOPP1 for redox balance (www.nature.com). Preliminary support for this comes from lab studies: VOPP1-overexpressing carcinoma cells underwent apoptosis when VOPP1 was knocked down or when ROS levels were increased without the counterbalance of VOPP1 (www.nature.com). Such insights could guide combination treatments (e.g. using pro-oxidant drugs or IκB stabilizers in VOPP1-high cancers).

In the context of autoimmune disease, the RA findings point to translational possibilities as well. If further validated, VOPP1 could be a novel therapeutic target in RA or other inflammatory conditions. The fact that VOPP1 knockdown reduced inflammatory cytokines in RA-FLS (pmc.ncbi.nlm.nih.gov) and improved arthritis in rats (pmc.ncbi.nlm.nih.gov) is encouraging. It suggests that drugs or biologics that suppress VOPP1 (or its downstream pathways like p38 MAPK) might ameliorate joint inflammation. While current RA treatments target broadly the immune system, a therapy directed at synovial fibroblast pathology (via VOPP1) could complement those by specifically curbing the aggressive behavior of these cells. However, any such approach would need to consider safety, given VOPP1’s wide normal expression. The “prosurvival” function of VOPP1 in normal cells (like perhaps in retina or other tissues (www.proteinatlas.org)) is not fully understood; systemic inhibition might have side effects if normal cells depend on VOPP1 under stress conditions. Despite that, the concept of targeting VOPP1 is now on the table both in oncology and immunology.

Real-world clinical implementation related to VOPP1 is still in early stages. No VOPP1-specific drugs or routine clinical tests are yet available, reflecting that VOPP1 was only relatively recently characterized. Nevertheless, its strong association with tumor survival signals has made it a subject of interest in cancer research. Some experimental therapeutics take an indirect approach – for instance, microRNA therapies or antisense oligonucleotides that restore tumor-suppressive miRNAs downregulating VOPP1 (like miR-218 in gastric cancer) are being explored in preclinical models (pubmed.ncbi.nlm.nih.gov). Additionally, VOPP1 might be considered in molecular diagnostic panels in the future. For example, if a patient’s tumor sequencing reveals EGFR amplification, adding an assay for VOPP1 expression or copy number could refine the molecular profile. In the case of the VOPP1::EGFR fusion found in a ganglioglioma, that discovery was made by advanced sequencing – going forward, pathologists might monitor for such fusions in unusual glioma cases (pmc.ncbi.nlm.nih.gov). In summary, while VOPP1 is not yet a household name in the clinic, it is gaining recognition as a meaningful biomolecule in disease. Efforts are ongoing to translate the growing understanding of VOPP1 into prognostic tools or targeted therapies.

Expert Commentary and Future Directions

Experts in the field underscore the importance of VOPP1 as a multifunctional regulator of cell survival. As early as 2011, researchers posited that “high-level, amplification-mediated ECOP expression… could contribute to resistance to apoptosis” in tumors with EGFR amplifications (www.nature.com). This insight positioned VOPP1 as part of the explanation for why certain cancers are harder to kill: it shifts the balance toward survival by amplifying NF-κB signals. Subsequent work by Baras et al. and others reinforced that VOPP1 overexpression is not an incidental byproduct of cancer genomics, but rather a functional player that cancer cells exploit (www.nature.com). By 2018, with the discovery of the VOPP1–WWOX interaction, commentators noted that VOPP1 behaves as a bona fide oncogene, in that it actively “promotes breast carcinogenesis by inhibiting the anti-tumoral effect of WWOX” (quote from Abu-Odeh et al., 2018) (bmcbiol.biomedcentral.com). A Frontiers in Oncology review highlighted VOPP1 among the “aberrantly expressed molecules” that can inhibit tumor suppressors like WWOX, pointing to a broader network of cancerous protein interactions (pmc.ncbi.nlm.nih.gov). Most recently, a comprehensive 2023 review of WWOX’s 25-year history stresses that VOPP1 has emerged as a significant regulator of WWOX and emphasizes that overexpression of VOPP1 is frequently observed in tumors and correlates with loss of WWOX function (pmc.ncbi.nlm.nih.gov). This evolution in expert perspective – from viewing VOPP1 as just a co-amplified gene to recognizing it as a central modulator of two major pathways (NF-κB and WWOX/p73) – validates the growing scientific interest in VOPP1.

Future research is expected to address several open questions about VOPP1. One area is the detailed molecular mechanism: How exactly does VOPP1 facilitate IκBα degradation and NF-κB activation? Does it recruit specific E3 ubiquitin ligases or kinases to the IκB complex, or perhaps affect endosomal signaling platforms for NF-κB? Another question is whether VOPP1 has any extracellular role – given its “secreted protein” annotation, could fragments of VOPP1 be released by cells (for example, in exosomes) and act on the tumor microenvironment? Also, the connection between VOPP1 and cellular metabolism warrants exploration. The WWOX interactome hints VOPP1 might link to metabolic organelles (ER, Golgi) and pathways (pubmed.ncbi.nlm.nih.gov). And intriguingly, the RA study suggested a metabolic intermediary (“X-23,587”) associated with VOPP1’s effect (pmc.ncbi.nlm.nih.gov), though this metabolite remains to be identified. Unraveling these links could reveal if VOPP1 influences metabolic stress or autophagy in cells.

On the clinical front, the challenge will be targeting VOPP1 safely. Experts caution that hitting a survival protein could affect normal cells, but the hope is that cancer cells (or rheumatoid synovium) might be more dependent on VOPP1 than healthy tissue, providing a therapeutic window. There is interest in developing peptides or small molecules to disrupt the VOPP1–WWOX interaction, effectively releasing the “brakes” on WWOX. Additionally, inhibitors of pathways downstream of VOPP1 (like NF-κB, p38 MAPK, or ROS homeostasis) could be tested in cases known to have high VOPP1. For example, combining an NF-κB pathway inhibitor with standard chemotherapy might preferentially kill VOPP1-driven tumors by removing their survival advantage. In RA, p38 inhibitors are already in trials; understanding that VOPP1 acts upstream of p38 in synoviocytes (pmc.ncbi.nlm.nih.gov) provides a rationale to revisit those therapies or develop more specific interventions at the VOPP1 level.

In conclusion, VOPP1 (Q96AW1) is an increasingly important gene in functional genomics, exemplifying how a relatively small vesicular protein can have wide-reaching effects on cell survival, inflammation, and tumor suppression. From its ability to turbo-charge NF-κB to its capacity to neutralize WWOX, VOPP1 sits at a crossroads of critical signaling pathways. Current research (particularly in the past few years) has expanded its relevance from cancer biology to immunology, and it stands out as a promising target for future therapeutic development. As always, translating these findings to the clinic will require careful validation and drug design, but the accumulating evidence – supported by diverse studies and expert analyses – positions VOPP1 as a novel “hub” protein whose modulation could yield benefits in treating cancer and inflammatory disease (bmcbiol.biomedcentral.com) (pmc.ncbi.nlm.nih.gov).

References: (Key sources with publication dates)

Citations

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  12. AnnotationURLCitation(end_index=3379, start_index=3208, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=tissues%20compared%20to%20matched%20normal,colocalization%20earlier%20reported%20for%20other')
  13. AnnotationURLCitation(end_index=4262, start_index=4127, title='ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner | Oncogene', type='url_citation', url='https://www.nature.com/articles/1208496#:~:text=In%20the%20present%20study%2C%20we,%CE%BAB%20activation%20by%20ECop')
  14. AnnotationURLCitation(end_index=4524, start_index=4389, title='ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner | Oncogene', type='url_citation', url='https://www.nature.com/articles/1208496#:~:text=In%20the%20present%20study%2C%20we,%CE%BAB%20activation%20by%20ECop')
  15. AnnotationURLCitation(end_index=4917, start_index=4754, title='ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner | Oncogene', type='url_citation', url='https://www.nature.com/articles/1208496#:~:text=activation%20confers%20cellular%20resistance%20to,contribute%20to%20resistance%20to%20apoptosis')
  16. AnnotationURLCitation(end_index=5166, start_index=5003, title='ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner | Oncogene', type='url_citation', url='https://www.nature.com/articles/1208496#:~:text=activation%20confers%20cellular%20resistance%20to,contribute%20to%20resistance%20to%20apoptosis')
  17. AnnotationURLCitation(end_index=5629, start_index=5480, title='ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner | Oncogene', type='url_citation', url='https://www.nature.com/articles/1208496#:~:text=decreased%20DNA%20binding%20of%20NF,contribute%20to%20resistance%20to%20apoptosis')
  18. AnnotationURLCitation(end_index=6348, start_index=6196, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=death%20at%2072%E2%80%89h%20post,abrogate%20the%20induction%20of%20apoptosis')
  19. AnnotationURLCitation(end_index=6483, start_index=6349, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=antioxidant%20N,by%20the%20intrinsic%20apoptotic%20pathway')
  20. AnnotationURLCitation(end_index=6792, start_index=6656, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=cancer%20types,affected%20by%20VOPP1%20knockdown%20exhibited')
  21. AnnotationURLCitation(end_index=7085, start_index=6933, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=death%20at%2072%E2%80%89h%20post,abrogate%20the%20induction%20of%20apoptosis')
  22. AnnotationURLCitation(end_index=7383, start_index=7233, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=showed%20that%20genes%20whose%20expression,SCC%20cell%20lines%20by%20VOPP1')
  23. AnnotationURLCitation(end_index=7735, start_index=7572, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=Reporters%20of%20reactive%20oxygen%20species,control%20of%20the%20intracellular%20redox')
  24. AnnotationURLCitation(end_index=8168, start_index=8034, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=antioxidant%20N,by%20the%20intrinsic%20apoptotic%20pathway')
  25. AnnotationURLCitation(end_index=8992, start_index=8821, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=tissues%20compared%20to%20matched%20normal,colocalization%20earlier%20reported%20for%20other')
  26. AnnotationURLCitation(end_index=9287, start_index=9116, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=tissues%20compared%20to%20matched%20normal,colocalization%20earlier%20reported%20for%20other')
  27. AnnotationURLCitation(end_index=9902, start_index=9752, title='Delineating WWOX Protein Interactome by Tandem Affinity Purification-Mass Spectrometry: Identification of Top Interactors and Key Metabolic Pathways Involved - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/30619736/#:~:text=key%20proteins%20from%20the%20endoplasmic,TCA%29%20cycle%20for%20energy')
  28. AnnotationURLCitation(end_index=10475, start_index=10317, title='Twenty-five years of WWOX insight in cancer: a treasure trove of knowledge - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12055895/#:~:text=of%20genes%20responsible%20for%20WWOX,WWOX%20and%20is%20associated%20with')
  29. AnnotationURLCitation(end_index=10701, start_index=10551, title='Delineating WWOX Protein Interactome by Tandem Affinity Purification-Mass Spectrometry: Identification of Top Interactors and Key Metabolic Pathways Involved - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/30619736/#:~:text=key%20proteins%20from%20the%20endoplasmic,TCA%29%20cycle%20for%20energy')
  30. AnnotationURLCitation(end_index=11034, start_index=10872, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=overexpressed%20in%20cancer%20pro,negative%2C%20tumors')
  31. AnnotationURLCitation(end_index=11394, start_index=11232, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=overexpressed%20in%20cancer%20pro,negative%2C%20tumors')
  32. AnnotationURLCitation(end_index=11855, start_index=11693, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=overexpressed%20in%20cancer%20pro,negative%2C%20tumors')
  33. AnnotationURLCitation(end_index=12130, start_index=11968, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=overexpressed%20in%20cancer%20pro,negative%2C%20tumors')
  34. AnnotationURLCitation(end_index=12689, start_index=12487, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=Overexpressed%20VOPP1%20potentiates%20cellular%20transformation,positive%2C%20but%20not%20with')
  35. AnnotationURLCitation(end_index=13003, start_index=12828, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=ability%20to%20associate%20with%20p73%CE%B1%2C,negative%2C%20tumors')
  36. AnnotationURLCitation(end_index=13364, start_index=13189, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=ability%20to%20associate%20with%20p73%CE%B1%2C,negative%2C%20tumors')
  37. AnnotationURLCitation(end_index=13652, start_index=13533, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=Conclusions')
  38. AnnotationURLCitation(end_index=14063, start_index=13905, title='Twenty-five years of WWOX insight in cancer: a treasure trove of knowledge - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12055895/#:~:text=of%20genes%20responsible%20for%20WWOX,WWOX%20and%20is%20associated%20with')
  39. AnnotationURLCitation(end_index=15054, start_index=14891, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=The%20vesicular%20overexpressed%20in%20cancer,that%20VOPP1%20knockdown%20induces%20cell')
  40. AnnotationURLCitation(end_index=15370, start_index=15221, title='ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner | Oncogene', type='url_citation', url='https://www.nature.com/articles/1208496#:~:text=decreased%20DNA%20binding%20of%20NF,contribute%20to%20resistance%20to%20apoptosis')
  41. AnnotationURLCitation(end_index=15621, start_index=15510, title='Expression of VOPP1 in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000154978-VOPP1/cancer#:~:text=TCGA%20,unfavorable')
  42. AnnotationURLCitation(end_index=16009, start_index=15837, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=fluorescent%20protein%20tagging%20and%20fluorescent,of%20ECOP%20in%20gastric%20adenocarcinoma')
  43. AnnotationURLCitation(end_index=16181, start_index=16010, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=tissues%20compared%20to%20matched%20normal,colocalization%20earlier%20reported%20for%20other')
  44. AnnotationURLCitation(end_index=16464, start_index=16292, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=fluorescent%20protein%20tagging%20and%20fluorescent,of%20ECOP%20in%20gastric%20adenocarcinoma')
  45. AnnotationURLCitation(end_index=16868, start_index=16697, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=tissues%20compared%20to%20matched%20normal,colocalization%20earlier%20reported%20for%20other')
  46. AnnotationURLCitation(end_index=17240, start_index=17069, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=tissues%20compared%20to%20matched%20normal,colocalization%20earlier%20reported%20for%20other')
  47. AnnotationURLCitation(end_index=17517, start_index=17381, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=cancer%20types,affected%20by%20VOPP1%20knockdown%20exhibited')
  48. AnnotationURLCitation(end_index=17899, start_index=17724, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=ability%20to%20associate%20with%20p73%CE%B1%2C,negative%2C%20tumors')
  49. AnnotationURLCitation(end_index=18125, start_index=17963, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=overexpressed%20in%20cancer%20pro,negative%2C%20tumors')
  50. AnnotationURLCitation(end_index=18624, start_index=18451, title='Expression of VOPP1 in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000154978-VOPP1/cancer#:~:text=PROGNOSTIC%20SUMMARY,significant%20%28p%3C1e%2B0%29%20PROTEIN%20EXPRESSION%5E%7Bi')
  51. AnnotationURLCitation(end_index=19130, start_index=18971, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=MicroRNAs%20are%20found%20to%20play,has%20been%20implicated%20in%20tumorigenesis')
  52. AnnotationURLCitation(end_index=19265, start_index=19131, title='LINC01410 Knockdown Suppresses Cervical Cancer Growth and Invasion via Targeting miR-2467-3p/VOPP1 Axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7008191/#:~:text=Targeting%20miR,3p%2FRGS17%20axis.%5E%7B28%7D%20At')
  53. AnnotationURLCitation(end_index=19888, start_index=19730, title='ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner | Oncogene', type='url_citation', url='https://www.nature.com/articles/1208496#:~:text=Ectopic%20expression%20of%20ECop%20increases,contribute%20to%20resistance%20to%20apoptosis')
  54. AnnotationURLCitation(end_index=20304, start_index=20131, title='LINC01410 Knockdown Suppresses Cervical Cancer Growth and Invasion via Targeting miR-2467-3p/VOPP1 Axis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7008191/#:~:text=LINC01410%20Knockdown%20Suppresses%20Cervical%20Cancer,3p%2FRGS17%20axis.%5E%7B28%7D%20At')
  55. AnnotationURLCitation(end_index=20719, start_index=20548, title='Twenty-five years of WWOX insight in cancer: a treasure trove of knowledge - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12055895/#:~:text=interest%20mapping%20to%20the%20chromosomal,advancements%20allowed%20to%20reveal%20its')
  56. AnnotationURLCitation(end_index=20878, start_index=20720, title='Twenty-five years of WWOX insight in cancer: a treasure trove of knowledge - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12055895/#:~:text=of%20genes%20responsible%20for%20WWOX,WWOX%20and%20is%20associated%20with')
  57. AnnotationURLCitation(end_index=21463, start_index=21327, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=cancer%20types,affected%20by%20VOPP1%20knockdown%20exhibited')
  58. AnnotationURLCitation(end_index=21743, start_index=21541, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=Overexpressed%20VOPP1%20potentiates%20cellular%20transformation,positive%2C%20but%20not%20with')
  59. AnnotationURLCitation(end_index=22824, start_index=22732, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=Results')
  60. AnnotationURLCitation(end_index=23297, start_index=23146, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=match%20at%20L358%20toward%20the,the%20data%20and%20we%20performed')
  61. AnnotationURLCitation(end_index=23651, start_index=23530, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=Western%20blot,FLSs%20%28Figure%203D')
  62. AnnotationURLCitation(end_index=24183, start_index=24056, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=Western%20blot%20%28Figure%206A%29,a%20p38')
  63. AnnotationURLCitation(end_index=24399, start_index=24272, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=Western%20blot%20%28Figure%206A%29,a%20p38')
  64. AnnotationURLCitation(end_index=24722, start_index=24595, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=Western%20blot%20%28Figure%206A%29,a%20p38')
  65. AnnotationURLCitation(end_index=25224, start_index=25074, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=match%20at%20L484%20treated%20with,23%2C587%20metabolism%2C%20and')
  66. AnnotationURLCitation(end_index=25853, start_index=25701, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=toward%20the%20VOPP1%20eQTL%20had,the%20data%20and%20we%20performed')
  67. AnnotationURLCitation(end_index=25981, start_index=25854, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=Western%20blot%20%28Figure%206A%29,a%20p38')
  68. AnnotationURLCitation(end_index=26446, start_index=26308, title='VOPP1::EGFR fusion is associated with NFκB pathway activation in a glioneural tumor with histological features of ganglioglioma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12001695/#:~:text=frequent%20one,provides%20a%20link%20to%20potentially')
  69. AnnotationURLCitation(end_index=26855, start_index=26717, title='VOPP1::EGFR fusion is associated with NFκB pathway activation in a glioneural tumor with histological features of ganglioglioma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12001695/#:~:text=frequent%20one,provides%20a%20link%20to%20potentially')
  70. AnnotationURLCitation(end_index=28194, start_index=28036, title='Twenty-five years of WWOX insight in cancer: a treasure trove of knowledge - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12055895/#:~:text=of%20genes%20responsible%20for%20WWOX,WWOX%20and%20is%20associated%20with')
  71. AnnotationURLCitation(end_index=28566, start_index=28395, title='Delineating WWOX Protein Interactome by Tandem Affinity Purification-Mass Spectrometry: Identification of Top Interactors and Key Metabolic Pathways Involved - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/30619736/#:~:text=biological%20and%20molecular%20processes%20while,acid%20degradation%20and%20other%20pathways')
  72. AnnotationURLCitation(end_index=29453, start_index=29280, title='Expression of VOPP1 in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000154978-VOPP1/cancer#:~:text=PROGNOSTIC%20SUMMARY,significant%20%28p%3C1e%2B0%29%20PROTEIN%20EXPRESSION%5E%7Bi')
  73. AnnotationURLCitation(end_index=29695, start_index=29520, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=ability%20to%20associate%20with%20p73%CE%B1%2C,negative%2C%20tumors')
  74. AnnotationURLCitation(end_index=30032, start_index=29861, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=tissues%20compared%20to%20matched%20normal,colocalization%20earlier%20reported%20for%20other')
  75. AnnotationURLCitation(end_index=30307, start_index=30148, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=MicroRNAs%20are%20found%20to%20play,has%20been%20implicated%20in%20tumorigenesis')
  76. AnnotationURLCitation(end_index=31217, start_index=31059, title='Twenty-five years of WWOX insight in cancer: a treasure trove of knowledge - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12055895/#:~:text=of%20genes%20responsible%20for%20WWOX,WWOX%20and%20is%20associated%20with')
  77. AnnotationURLCitation(end_index=31787, start_index=31653, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=antioxidant%20N,by%20the%20intrinsic%20apoptotic%20pathway')
  78. AnnotationURLCitation(end_index=32147, start_index=31997, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=showed%20that%20genes%20whose%20expression,SCC%20cell%20lines%20by%20VOPP1')
  79. AnnotationURLCitation(end_index=32682, start_index=32555, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=Western%20blot%20%28Figure%206A%29,a%20p38')
  80. AnnotationURLCitation(end_index=32864, start_index=32714, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=match%20at%20L484%20treated%20with,23%2C587%20metabolism%2C%20and')
  81. AnnotationURLCitation(end_index=33587, start_index=33419, title='Expression of VOPP1 in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000154978-VOPP1/cancer#:~:text=HUMAN%20PROTEIN%20ATLAS%20INFORMATION,i%7D%20Evidence%20at%20protein%20level')
  82. AnnotationURLCitation(end_index=34574, start_index=34415, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=MicroRNAs%20are%20found%20to%20play,has%20been%20implicated%20in%20tumorigenesis')
  83. AnnotationURLCitation(end_index=35165, start_index=35027, title='VOPP1::EGFR fusion is associated with NFκB pathway activation in a glioneural tumor with histological features of ganglioglioma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12001695/#:~:text=frequent%20one,provides%20a%20link%20to%20potentially')
  84. AnnotationURLCitation(end_index=35900, start_index=35751, title='ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner | Oncogene', type='url_citation', url='https://www.nature.com/articles/1208496#:~:text=decreased%20DNA%20binding%20of%20NF,contribute%20to%20resistance%20to%20apoptosis')
  85. AnnotationURLCitation(end_index=36398, start_index=36264, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=antioxidant%20N,by%20the%20intrinsic%20apoptotic%20pathway')
  86. AnnotationURLCitation(end_index=36785, start_index=36666, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=Conclusions')
  87. AnnotationURLCitation(end_index=37169, start_index=36995, title='Cancerous Protein Network That Inhibits the Tumor Suppressor Function of WW Domain-Containing Oxidoreductase (WWOX) by Aberrantly Expressed Molecules - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6125347/#:~:text=Cancerous%20Protein%20Network%20That%20Inhibits,the%20WWOX%20tumor%20suppressor%20function')
  88. AnnotationURLCitation(end_index=37594, start_index=37436, title='Twenty-five years of WWOX insight in cancer: a treasure trove of knowledge - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12055895/#:~:text=of%20genes%20responsible%20for%20WWOX,WWOX%20and%20is%20associated%20with')
  89. AnnotationURLCitation(end_index=38728, start_index=38557, title='Delineating WWOX Protein Interactome by Tandem Affinity Purification-Mass Spectrometry: Identification of Top Interactors and Key Metabolic Pathways Involved - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/30619736/#:~:text=biological%20and%20molecular%20processes%20while,acid%20degradation%20and%20other%20pathways')
  90. AnnotationURLCitation(end_index=38957, start_index=38840, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=match%20at%20L400%20and%203,5908')
  91. AnnotationURLCitation(end_index=40100, start_index=39973, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=Western%20blot%20%28Figure%206A%29,a%20p38')
  92. AnnotationURLCitation(end_index=41206, start_index=41087, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=Conclusions')
  93. AnnotationURLCitation(end_index=41334, start_index=41207, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=Western%20blot%20%28Figure%206A%29,a%20p38')
  94. AnnotationURLCitation(end_index=41659, start_index=41488, title='Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25398664/#:~:text=tissues%20compared%20to%20matched%20normal,colocalization%20earlier%20reported%20for%20other')
  95. AnnotationURLCitation(end_index=41846, start_index=41738, title='ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner | Oncogene', type='url_citation', url='https://www.nature.com/articles/1208496#:~:text=In%20the%20present%20study%2C%20we,level')
  96. AnnotationURLCitation(end_index=42010, start_index=41847, title='ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner | Oncogene', type='url_citation', url='https://www.nature.com/articles/1208496#:~:text=activation%20confers%20cellular%20resistance%20to,contribute%20to%20resistance%20to%20apoptosis')
  97. AnnotationURLCitation(end_index=42266, start_index=42114, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=death%20at%2072%E2%80%89h%20post,abrogate%20the%20induction%20of%20apoptosis')
  98. AnnotationURLCitation(end_index=42401, start_index=42267, title='Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury | Laboratory Investigation', type='url_citation', url='https://www.nature.com/articles/labinvest201170#:~:text=antioxidant%20N,by%20the%20intrinsic%20apoptotic%20pathway')
  99. AnnotationURLCitation(end_index=42666, start_index=42504, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=overexpressed%20in%20cancer%20pro,negative%2C%20tumors')
  100. AnnotationURLCitation(end_index=42842, start_index=42667, title='VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX | BMC Biology | Full Text', type='url_citation', url='https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0576-6#:~:text=ability%20to%20associate%20with%20p73%CE%B1%2C,negative%2C%20tumors')
  101. AnnotationURLCitation(end_index=43114, start_index=42943, title='Delineating WWOX Protein Interactome by Tandem Affinity Purification-Mass Spectrometry: Identification of Top Interactors and Key Metabolic Pathways Involved - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/30619736/#:~:text=biological%20and%20molecular%20processes%20while,acid%20degradation%20and%20other%20pathways')
  102. AnnotationURLCitation(end_index=43368, start_index=43230, title='VOPP1::EGFR fusion is associated with NFκB pathway activation in a glioneural tumor with histological features of ganglioglioma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12001695/#:~:text=frequent%20one,provides%20a%20link%20to%20potentially')
  103. AnnotationURLCitation(end_index=43606, start_index=43479, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=Western%20blot%20%28Figure%206A%29,a%20p38')
  104. AnnotationURLCitation(end_index=43757, start_index=43607, title='VOPP1 as a Novel Susceptibility Gene in Rheumatoid Arthritis: Insights Into Its Mechanisms From Mendelian Randomization and Experimental Validation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12327419/#:~:text=match%20at%20L484%20treated%20with,23%2C587%20metabolism%2C%20and')
  105. AnnotationURLCitation(end_index=44010, start_index=43837, title='Expression of VOPP1 in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000154978-VOPP1/cancer#:~:text=PROGNOSTIC%20SUMMARY,significant%20%28p%3C1e%2B0%29%20PROTEIN%20EXPRESSION%5E%7Bi')
  106. AnnotationURLCitation(end_index=44179, start_index=44011, title='Expression of VOPP1 in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000154978-VOPP1/cancer#:~:text=HUMAN%20PROTEIN%20ATLAS%20INFORMATION,i%7D%20Evidence%20at%20protein%20level')
  107. AnnotationURLCitation(end_index=44434, start_index=44270, title='VOPP1 Gene - GeneCards | VOPP1 Protein | VOPP1 Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=VOPP1#:~:text=Increases%20the%20transcriptional%20activity%20of,%28%20VOPP1_HUMAN%2CQ96AW1')