KCTD11 (REN/KCASH1) – Structure, Function, and Biological Significance

Gene and Protein Overview

KCTD11 (Potassium Channel Tetramerization Domain-containing protein 11) is a human gene located on chromosome 17p13.2 that encodes a BTB/POZ domain-containing protein (pmc.ncbi.nlm.nih.gov) (www.proteinatlas.org). Originally identified in neural development studies, KCTD11 (also known by aliases REN and KCASH1) was found to be expressed in differentiating, low-proliferation neural progenitors and absent in rapidly dividing neuroblasts (pmc.ncbi.nlm.nih.gov). It encodes a 246-amino-acid intracellular protein confirmed at the protein level (www.proteinatlas.org). KCTD11 belongs to the broader KCTD family of proteins, which share a conserved BTB (Broad-Complex, Tramtrack, Bric-à-brac)/POZ domain at the N-terminus and are capable of forming oligomeric complexes and acting as substrate adaptors for ubiquitin ligases (biosignaling.biomedcentral.com).

Key structural features: The N-terminal BTB/POZ domain of KCTD11 mediates homo-oligomerization (identical protein binding) and recruitment of CUL3, a Cullin-3 RING ubiquitin ligase scaffold (biosignaling.biomedcentral.com). This allows KCTD11 to function as a substrate-recognition subunit of a CUL3-based E3 ubiquitin ligase complex (sometimes denoted CRL3^REN) (www.nature.com). The C-terminus of KCTD11 (sometimes annotated as the KCTD11/21_C domain) is unique to the KCTD11/21 subfamily and is thought to confer specificity for binding target proteins. KCTD11 lacks known enzymatic motifs; instead, its biological activity derives from serving as an adaptor protein that links target substrates to the ubiquitination machinery (biosignaling.biomedcentral.com). Notably, KCTD11 is one of three closely related BTB-domain adaptors (with KCTD21 and KCTD6) collectively termed the KCASH (KCTD Containing Cullin3 Adaptors Suppressors of Hedgehog) family (biosignaling.biomedcentral.com).

Cellular Localization and Expression Patterns

KCTD11 is an intracellular protein found in both the cytoplasm and nucleus, with predominant localization to the nucleoplasm (www.proteinatlas.org). This nuclear presence aligns with its role in regulating gene expression pathways (see below). The gene is broadly expressed across tissues (low tissue-specificity), with mRNA and protein detectable in many cell types (www.proteinatlas.org). Importantly, brain expression is significant: KCTD11 levels are highest in the cerebellum compared to other brain regions (pmc.ncbi.nlm.nih.gov). During embryonic development, KCTD11 expression is tightly regulated – it is enriched in differentiating neural precursors of the brain’s ventricular zone and largely absent in proliferating neuroblasts (pmc.ncbi.nlm.nih.gov). Consistent with this, experimental studies showed that introducing KCTD11 causes growth arrest and neuronal differentiation in cerebellar progenitor cells (pmc.ncbi.nlm.nih.gov). Thus, under normal physiological conditions KCTD11 helps restrain cell proliferation and promote maturation, particularly in the nervous system (reflected by gene ontology annotations of positive regulation of neuron differentiation and negative regulation of neuroblast proliferation (www.ncbi.nlm.nih.gov)).

In adult tissues, KCTD11 protein is found at moderate levels in most organs. Immunohistochemistry and transcript profiling confirm mixed cytoplasmic/nuclear expression in a variety of cell types, including epithelial cells and glial cells (www.proteinatlas.org). It is not secreted or membrane-bound, in line with its role as an intracellular signaling regulator (www.proteinatlas.org). The widespread but controlled expression of KCTD11 suggests it performs a fundamental cellular function, and disruptions of its expression can have pathological consequences (discussed below).

Mechanism of Action: Cullin-3 Adaptor and Hedgehog Pathway Suppressor

KCTD11’s best-characterized function is as a negative regulator of the Sonic Hedgehog (SHH) signaling pathway, a crucial pathway in embryonic development and cell proliferation. KCTD11 was initially identified as a tumor suppressor frequently lost in medulloblastoma (a pediatric cerebellar tumor), where aberrant Hedgehog signaling drives cancer growth (pmc.ncbi.nlm.nih.gov). Early studies demonstrated that loss of KCTD11 (REN) in medulloblastoma leads to unchecked activity of the Hedgehog effector GLI1, whereas restoring KCTD11 inhibits tumor cell proliferation by antagonizing GLI1-mediated transcription (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In other words, KCTD11 was established as a suppressor of the SHH–Gli pathway, whose inactivation contributes to tumorigenesis in the cerebellum (pmc.ncbi.nlm.nih.gov).

Biochemical function: KCTD11 acts as the substrate-recognition subunit of a Cullin-3/RING E3 ubiquitin ligase complex (CRL3^KCTD11) (www.nature.com). Through its BTB domain, KCTD11 binds to the CUL3 scaffold, positioning specific target proteins for ubiquitination. The primary substrate identified for CRL3^KCTD11 is Histone Deacetylase 1 (HDAC1) (biosignaling.biomedcentral.com). KCTD11 directly interacts with HDAC1 and promotes its polyubiquitination and proteasomal degradation (biosignaling.biomedcentral.com). HDAC1 is an enzyme that normally removes acetyl groups from histones and other proteins; in the context of Hedgehog signaling, HDAC1 is known to deacetylate the GLI1 transcription factor, a modification required for GLI1’s full activity (biosignaling.biomedcentral.com). By targeting HDAC1 for degradation, KCTD11 causes HDAC1 levels to drop, which in turn leads to hyper-acetylation of GLI1 (biosignaling.biomedcentral.com). Acetylated GLI1 is unable to effectively activate Hedgehog target genes, thereby blocking Hedgehog pathway signaling (biosignaling.biomedcentral.com). This mechanism was elucidated in a 2010 study showing that the interplay between the KCTD11–CUL3 ubiquitin ligase and HDAC1 controls GLI1 acetylation status and transcriptional activity (biosignaling.biomedcentral.com) (biosignaling.biomedcentral.com). In cerebellar granule cell progenitors, the net effect of KCTD11 expression is to induce cell-cycle exit, neuronal differentiation, and apoptosis – essentially counteracting the mitogenic effects of Sonic Hedgehog signals (biosignaling.biomedcentral.com).

Additional substrates and interactions: More recent research has expanded the understanding of KCTD11’s role in Hedgehog signaling. In 2023, Infante et al. identified the stemness factor SALL4 as a novel target of the KCTD11–CUL3 E3 complex (www.nature.com). SALL4 is a transcription factor that is abnormally re-expressed in SHH-driven medulloblastomas and correlates with worse patient survival (www.nature.com). Proteomic analysis revealed that KCTD11 (REN) binds SALL4 and induces ubiquitination-dependent degradation of SALL4 (specifically, wild-type SALL4 but not mutants lacking a certain zinc-finger domain) (www.nature.com). This finding is significant because SALL4 binds to GLI1 and recruits HDAC1, forming a complex that deacetylates GLI1 to enhance its activity (www.nature.com). Thus, KCTD11 imposes a double restraint on Hedgehog signaling: it eliminates HDAC1 and eliminates SALL4, both of which are required to keep GLI1 in a deacetylated (active) state (www.nature.com). In the absence of KCTD11, SALL4 and HDAC1 collaborate to hyperactivate GLI1, driving uncontrolled cell proliferation. The discovery of SALL4 as a CRL3^KCTD11 substrate provides a mechanistic explanation for how loss of KCTD11 leads to aggressive SHH-medulloblastomas (www.nature.com). Indeed, approximately 30–50% of SHH-subtype medulloblastomas exhibit loss of KCTD11 function – either through allelic deletion on 17p13.2 or epigenetic silencing – underscoring its role as a major tumor suppressor in this context (www.nature.com) (biosignaling.biomedcentral.com).

It is worth noting that KCTD11 can form heteromeric complexes with its paralogs KCTD6 (KCASH3) and KCTD21 (KCASH2), which are also Cullin3 adaptors that inhibit Hedgehog signaling (biosignaling.biomedcentral.com) (biosignaling.biomedcentral.com). These three proteins share structural features and often act in concert. For example, KCTD6 alone cannot bind HDAC1, but when it heterodimerizes with KCTD11, the complex can still target HDAC1 for degradation (biosignaling.biomedcentral.com). This suggests a cooperative tumor-suppressive network, wherein multiple KCTD adaptors ensure robust repression of the Hedgehog pathway. Together, KCTD11/21/6 (the KCASH family) serve as redundant brakes on SHH signaling during normal cerebellar development and are frequently inactivated in Hh-driven tumors (biosignaling.biomedcentral.com) (biosignaling.biomedcentral.com).

Involvement in Other Signaling Pathways and Cellular Processes

While Hedgehog pathway regulation is the primary known function of KCTD11, emerging evidence shows that KCTD11 influences other oncogenic signaling pathways, highlighting a broader role in maintaining cellular homeostasis:

• Wnt/β-Catenin Pathway: Studies in cancer models have revealed a link between KCTD11 and the Wnt signaling cascade. In non-small cell lung cancer (NSCLC) cells, KCTD11 was found to physically interact with β-catenin (the key transcriptional co-activator in canonical Wnt signaling) (pubmed.ncbi.nlm.nih.gov). Through this interaction, KCTD11 inhibits the nuclear translocation of β-catenin, thereby suppressing Wnt target gene activation (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Experimental overexpression of KCTD11 in NSCLC cell lines led to a significant decrease in Wnt pathway activity (as measured by a TOPflash β-catenin/Tcf reporter assay) and reduced levels of nuclear β-catenin (pubmed.ncbi.nlm.nih.gov). Conversely, siRNA-mediated knockdown of KCTD11 caused an upregulation of Wnt signaling activity (pubmed.ncbi.nlm.nih.gov). By keeping β-catenin out of the nucleus, KCTD11 effectively dampens Wnt-driven transcription of genes involved in proliferation and epithelial-mesenchymal transition (EMT). In line with this, KCTD11 re-expression reversed EMT markers in lung cancer cells: E-cadherin and ZO-1 (epithelial markers) increased, while N-cadherin, vimentin, Snail, and Slug (mesenchymal and EMT-inducing factors) were downregulated (pubmed.ncbi.nlm.nih.gov). Functionally, KCTD11 suppressed the malignant phenotype – reducing NSCLC cell proliferation, invasion, and colony formation, whereas loss of KCTD11 had the opposite effect (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). These findings (Yang et al., J. Cell. Mol. Med. 2021) position KCTD11 as an inhibitor of the Wnt/β-catenin pathway in at least some contexts, achieved by sequestering or destabilizing β-catenin in the cytoplasm. Interestingly, KCTD11’s BTB domain was required for these effects, suggesting the involvement of its ubiquitin-ligase function in modulating Wnt components (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov) (possibly through polyubiquitination of β-catenin or associated regulators, though β-catenin degradation was not explicitly shown in this study).

• Hippo/YAP Pathway: KCTD11 is also implicated in the Hippo signaling pathway, which controls organ size and cell proliferation via the transcriptional co-activator YAP. In lung cancer cells, KCTD11 overexpression was shown to reduce the nuclear accumulation of YAP in parallel with β-catenin (pubmed.ncbi.nlm.nih.gov). YAP and β-catenin often cooperate to drive oncogenic transcription, and KCTD11’s ability to retain both factors in the cytoplasm indicates a coordinated suppression of proliferative signaling (pubmed.ncbi.nlm.nih.gov). In support of this, KCTD11-low NSCLC tumors exhibited higher rates of EMT and metastasis, phenomena typically associated with concurrent Wnt and Hippo pathway activation (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). A separate study in hepatocellular carcinoma (HCC) provides further evidence that KCTD11 activates the Hippo pathway, reinforcing its tumor-suppressive role. Tong et al. (Oncotarget, 2017) reported that KCTD11 is downregulated in HCC, and low expression correlates with shorter patient survival (www.oncotarget.com). Restoring KCTD11 in HCC cells led to increased phosphorylation (activation) of Hippo pathway kinases and functional inactivation of YAP (the downstream effector), as indicated by reduced levels of YAP target genes like CTGF (Connective Tissue Growth Factor) (www.oncotarget.com). Through Hippo pathway activation, KCTD11 induces the cell cycle inhibitor p21 (potentially via stabilization of p53 and activation of MST1 kinase) and triggers cellular senescence or arrest (www.oncotarget.com). In vivo, KCTD11 re-expression slowed HCC tumor growth and metastasis in mouse models (www.oncotarget.com). Molecular analyses showed that KCTD11 decreased pro-metastatic factors (such as MMPs and Claudin-1) and mesenchymal markers, thereby suppressing EMT and invasion (www.oncotarget.com). Notably, Cldn1 and CTGF are direct targets of YAP/TAZ, so their reduction confirms that KCTD11 is effectively turning on Hippo signaling to keep YAP in check (www.oncotarget.com). These data from lung and liver cancers indicate that KCTD11’s tumor-suppressive activity is not limited to Hedgehog pathway inhibition – it also extends to other major growth and differentiation pathways (Wnt and Hippo), likely by promoting the degradation or cytoplasmic retention of key regulators (β-catenin and YAP). In summary, KCTD11 serves as a multi-pathway suppressor of oncogenic signaling, aligning with its frequent loss in diverse tumor types.

Role in Development and Disease

Developmental function: In normal development, KCTD11’s role as a brake on Hedgehog signaling is important for proper patterning and differentiation in the brain. Sonic Hedgehog is required for the proliferation of granule neuron precursors in the developing cerebellum; KCTD11 provides a counterbalance that ensures these cells exit the cell cycle and differentiate at the appropriate time (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Mice with disrupted Hedgehog antagonists often develop cerebellar overgrowth or tumors, underscoring the significance of regulators like KCTD11. While a complete KCTD11 knockout model has not been widely reported in literature, in vitro studies of neural progenitors clearly show that KCTD11 induction causes cessation of proliferation and promotes neuronal differentiation and apoptosis of precursor cells (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Additionally, KCTD11 (KCASH1) is highly expressed in the postnatal cerebellum, suggesting it contributes to the normal maturation of this brain region (biosignaling.biomedcentral.com). Its induction has also been observed in other differentiation contexts (e.g. peri-ovulatory ovarian cells in rodents), implying a broader role in driving cells towards a differentiated state (biosignaling.biomedcentral.com) (biosignaling.biomedcentral.com).

Tumor suppressor in cancer: KCTD11 is now recognized as a bona fide tumor suppressor gene in humans. Its inactivation is associated with several cancer types, most prominently in SHH-driven medulloblastoma but also in others such as prostate, liver, and lung tumors. In medulloblastoma (MB), the loss of one copy of KCTD11 (17p13 deletion encompassing the KCTD11 locus) is the single most frequent genetic lesion in the SHH subtype, occurring in roughly 30–50% of cases (biosignaling.biomedcentral.com) (www.nature.com). This partial loss (haploinsufficiency) leads to substantially reduced KCTD11 mRNA and protein levels in tumors compared to normal cerebellar tissue (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Even MB tumors without a gross deletion often show dramatically lowered KCTD11 expression due to epigenetic mechanisms (molecular-cancer.biomedcentral.com) (molecular-cancer.biomedcentral.com). Indeed, the promoter region of KCTD11 is a CpG island that is frequently hypermethylated in cancer cell lines and primary tumors, silencing gene transcription (molecular-cancer.biomedcentral.com) (molecular-cancer.biomedcentral.com). Treatment of cancer cells with DNA demethylating agents (5-azacytidine) can reactivate KCTD11 expression, confirming that DNA methylation directly represses KCTD11 in many tumors (molecular-cancer.biomedcentral.com) (molecular-cancer.biomedcentral.com). Additionally, the transcription factor Sp1 has been shown to bind the KCTD11 promoter and protect it from methylation; loss of Sp1 binding or Sp1 inactivation may thus predispose the KCTD11 locus to epigenetic silencing (molecular-cancer.biomedcentral.com) (molecular-cancer.biomedcentral.com). Through a combination of deletion and methylation, KCTD11 is widely downregulated in human cancers (molecular-cancer.biomedcentral.com). For example, studies report reduced KCTD11 expression in prostate carcinoma, colorectal cancer, gastric cancer, breast cancer, lung cancer, bladder cancer, and others (biosignaling.biomedcentral.com). An analysis by Zazzeroni et al. (2014) found significantly lower KCTD11 levels in a broad panel of solid tumors compared to normal tissues (biosignaling.biomedcentral.com). The consistent loss of KCTD11 in cancers aligns with its role in restraining pro-proliferative pathways (Hedgehog, Wnt, YAP). When KCTD11 function is lost, these pathways can become overactive, contributing to uncontrolled growth, survival, and stem-like properties of cancer cells.

Clinically, low KCTD11 expression is associated with more aggressive disease and poorer prognosis in multiple cancers. In medulloblastoma patients, KCTD11 loss (via 17p deletion or low mRNA) correlates with higher-grade tumors and possibly treatment resistance (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In glioblastoma multiforme (GBM), The Human Protein Atlas reports that KCTD11 is a favorable prognostic marker (higher expression linked to better survival) (www.proteinatlas.org). Similarly, immunohistochemistry on NSCLC patient samples (n = 139) showed that low KCTD11 levels significantly correlated with advanced tumor stage, poor differentiation, and lymph node metastasis (pmc.ncbi.nlm.nih.gov). NSCLC patients lacking KCTD11 had worse overall survival on follow-up, indicating its potential use as a prognostic biomarker in lung cancer (pmc.ncbi.nlm.nih.gov). In hepatocellular carcinoma, analysis of 112 cases found that those with low KCTD11 had shorter survival, and multivariate Cox analysis identified KCTD11 expression as an independent prognostic factor (www.oncotarget.com). These data underscore that restoration of KCTD11 tends to suppress tumor progression, whereas its absence exacerbates malignancy.

Current Research Directions and Therapeutic Implications

Given KCTD11’s central role in tumor suppression and pathway regulation, it is drawing interest as a potential diagnostic marker and therapeutic target. Experts have suggested that assessing KCTD11 (KCASH1) expression could aid in cancer prognosis or subtype classification – for instance, SHH-subtype medulloblastomas often coincide with KCASH1/KCTD11 downregulation (biosignaling.biomedcentral.com), and re-expression of KCTD11 might serve as a marker of treatment-induced differentiation. Moreover, reactivating or substituting KCTD11 function in tumors is a concept under exploration. Because KCTD11 itself is not an enzyme, drug strategies focus on upstream and downstream elements: for example, epigenetic drugs (DNA methylation inhibitors or histone acetylation modulators) might be used to demethylate the KCTD11 promoter and restore its expression in tumors where it is silenced (molecular-cancer.biomedcentral.com) (molecular-cancer.biomedcentral.com). In a 2010 study, demethylating colon cancer cells led to a significant increase in KCTD11 mRNA, providing proof-of-principle that epigenetic therapy can upregulate this tumor suppressor (molecular-cancer.biomedcentral.com). Another avenue is targeting the pathways and substrates affected by KCTD11. For instance, the newly identified SALL4–HDAC1–GLI1 axis offers a therapeutic opportunity: even if KCTD11 is lost, inhibiting SALL4 or HDAC1 could mimic KCTD11’s effect and shut down Hedgehog signaling. In fact, the 2023 study showed that pharmacological or genetic inhibition of SALL4 suppressed SHH-medulloblastoma growth in mouse and patient-derived models (www.nature.com). Thus, SALL4 is proposed as a drug target in KCTD11-deficient tumors (www.nature.com). Similarly, in KCTD11-low cancers that show Wnt activation, β-catenin pathway inhibitors might be particularly effective, and in those with YAP overactivity, Hippo pathway activators or YAP inhibitors could be beneficial. Research is ongoing to map the full network of KCTD11 interactions – for example, structural studies (using AlphaFold and cryo-EM) are investigating how KCTD11 assembles into oligomers and binds CUL3 and substrates (biosignaling.biomedcentral.com) (biosignaling.biomedcentral.com). Understanding these interfaces could inform the design of stapled peptides or small molecules that stabilize the KCTD11–CUL3–substrate complex or otherwise enhance its activity.

Expert perspective: Comprehensive reviews of the KCTD protein family highlight KCTD11 as a prototypical tumor suppressor whose loss promotes oncogenesis (biosignaling.biomedcentral.com) (biosignaling.biomedcentral.com). Researchers Di Marcotullio et al. (who first characterized KCTD11) emphasize that KCTD11/KCASH1 is a critical inhibitor of Hh-driven tumorigenesis, and they note that strategies to increase its expression could have therapeutic value in Hedgehog-dependent cancers (biosignaling.biomedcentral.com). Additionally, bioinformatics analyses (COSMIC and TCGA data) have reinforced that KCTD11 is frequently under-expressed in malignancies – for example, one study found KCTD11 mRNA downregulated in ~60% of ovarian carcinoma cases examined (biosignaling.biomedcentral.com). Such findings position KCTD11 as not only a subject of fundamental scientific interest but also a candidate biomarker for cancer diagnosis/prognosis and a node in critical signaling pathways that new drugs might exploit.

In summary, KCTD11 (REN/KCASH1) is a multifaceted protein that serves as a Cullin-3 adaptor to restrain key growth signals in cells. It localizes to the nucleus to mediate ubiquitination of specific substrates (HDAC1, SALL4, etc.), thereby enforcing transcriptional programs that favor differentiation and cell cycle exit. Loss of KCTD11 unleashes developmental pathways like Hedgehog, Wnt, and YAP, contributing to tumor development. Current research (especially from 2017–2024) has broadened our understanding of KCTD11’s interactome and paved the way for translational approaches – for instance, targeting the SALL4–HDAC1–GLI1 circuit in Hedgehog-driven tumors or using KCTD11 expression levels as a predictive clinical marker (www.nature.com) (pmc.ncbi.nlm.nih.gov). As we continue to decode the KCTD11 protein’s functions, it stands out as a crucial regulator of cellular growth and a promising point of intervention in diseases where this regulation fails.

Sources: Comprehensive information was compiled from recent reviews and primary research articles, including a 2021 review on KCTD proteins in cancer (biosignaling.biomedcentral.com) (biosignaling.biomedcentral.com), original studies from 2004–2010 that established KCTD11’s role in Hedgehog signaling (pmc.ncbi.nlm.nih.gov) (biosignaling.biomedcentral.com), and the latest research from 2017–2023 uncovering its interactions with β-catenin, YAP, and SALL4 (pubmed.ncbi.nlm.nih.gov) (www.nature.com). These sources and others are cited in-line to document the current understanding of KCTD11’s function, regulation, and significance in human biology and disease. Each citation includes a URL and reference to the publication or database for verification of the stated findings.

Citations

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21. AnnotationURLCitation(end_index=7603, start_index=7437, title='RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC490020/#:~:text=in%20vitro%20and%20suppresses%20xenograft,its%20growth%20inhibitory%20activity%20is')
22. AnnotationURLCitation(end_index=7881, start_index=7746, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=that%20SALL4%20interacts%20with%20REN%2FKCTD11,dependent')
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24. AnnotationURLCitation(end_index=8468, start_index=8330, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=as%20REN,22%2C%2013')
25. AnnotationURLCitation(end_index=8845, start_index=8707, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=as%20REN,22%2C%2013')
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27. AnnotationURLCitation(end_index=9375, start_index=9237, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=as%20REN,22%2C%2013')
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29. AnnotationURLCitation(end_index=9883, start_index=9702, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=signalling%3A%20binding%20to%20Cul3%2C%20they,12%20%2C%20%2023')
30. AnnotationURLCitation(end_index=10249, start_index=10107, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=KCASH1,58%20%2C%20%2072')
31. AnnotationURLCitation(end_index=10638, start_index=10503, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=that%20SALL4%20interacts%20with%20REN%2FKCTD11,dependent')
32. AnnotationURLCitation(end_index=10938, start_index=10778, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=show%20that%20the%20pro,potentiate%20GLI1%20deacetylation%20and%20transcriptional')
33. AnnotationURLCitation(end_index=11276, start_index=11141, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=that%20SALL4%20interacts%20with%20REN%2FKCTD11,dependent')
34. AnnotationURLCitation(end_index=11550, start_index=11423, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=lost%20in%20~30,MB%20growth%20both%20in%20murine')
35. AnnotationURLCitation(end_index=11842, start_index=11738, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=lost%20in%20~30,dependent')
36. AnnotationURLCitation(end_index=12248, start_index=12111, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=4%20%28SALL4%29%20is%20re,MB%20growth%20both%20in%20murine')
37. AnnotationURLCitation(end_index=12625, start_index=12488, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=4%20%28SALL4%29%20is%20re,MB%20growth%20both%20in%20murine')
38. AnnotationURLCitation(end_index=12824, start_index=12626, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=Interestingly%2C%20among%20the%20genetic%20alterations,72%2C%2061%20%2C%20%2075')
39. AnnotationURLCitation(end_index=13208, start_index=13016, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=structural%20and%20functional%20features%20in,and%20thus%20blocking%20its')
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41. AnnotationURLCitation(end_index=13724, start_index=13572, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=68%20%5D%2C%20neuroblastoma%20,84')
42. AnnotationURLCitation(end_index=14233, start_index=14038, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=Group%20B%20is%20composed%20of,the%20ubiquitination%20and%20degradation%20of')
43. AnnotationURLCitation(end_index=14384, start_index=14234, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=KCASH2,12%20%2C%20%2025%2C%2066')
44. AnnotationURLCitation(end_index=15112, start_index=14972, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20%CE%B2,the%20Wnt%20and%20Hippo%20pathways')
45. AnnotationURLCitation(end_index=15387, start_index=15247, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20%CE%B2,the%20Wnt%20and%20Hippo%20pathways')
46. AnnotationURLCitation(end_index=15538, start_index=15388, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20the%20Wnt%20pathway,The%20experiment%20is%20treated')
47. AnnotationURLCitation(end_index=15899, start_index=15749, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20the%20Wnt%20pathway,The%20experiment%20is%20treated')
48. AnnotationURLCitation(end_index=16147, start_index=15997, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20the%20Wnt%20pathway,The%20experiment%20is%20treated')
49. AnnotationURLCitation(end_index=16744, start_index=16563, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20the%20process%20of,Slug%20are%20downregulated%20in%20KCTD11%E2%80%90overexpressing')
50. AnnotationURLCitation(end_index=17106, start_index=16922, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20proliferation%20and%20invasion,cells%20are%20increased%20in%20KCTD11%E2%80%90depleted')
51. AnnotationURLCitation(end_index=17257, start_index=17107, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20the%20Wnt%20pathway,The%20experiment%20is%20treated')
52. AnnotationURLCitation(end_index=17839, start_index=17633, title='KCTD11 inhibits progression of lung cancer by binding to β‐catenin to regulate the activity of the Wnt and Hippo pathways - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8500973/#:~:text=KCTD11%C2%A0has%20been%20reported%20to%20be,assay%2C%20RT%E2%80%90qPCR%2C%20immunofluorescence%20and%20immunoprecipitation')
53. AnnotationURLCitation(end_index=17980, start_index=17840, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20%CE%B2,the%20Wnt%20and%20Hippo%20pathways')
54. AnnotationURLCitation(end_index=18569, start_index=18429, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20%CE%B2,the%20Wnt%20and%20Hippo%20pathways')
55. AnnotationURLCitation(end_index=18903, start_index=18763, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20%CE%B2,the%20Wnt%20and%20Hippo%20pathways')
56. AnnotationURLCitation(end_index=19215, start_index=19075, title='KCTD11 inhibits progression of lung cancer by binding to β-catenin to regulate the activity of the Wnt and Hippo pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34453479/#:~:text=KCTD11%20inhibits%20%CE%B2,the%20Wnt%20and%20Hippo%20pathways')
57. AnnotationURLCitation(end_index=19393, start_index=19216, title='KCTD11 inhibits progression of lung cancer by binding to β‐catenin to regulate the activity of the Wnt and Hippo pathways - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8500973/#:~:text=clinicopathological%20factors%20in%20patients%20with,age%2C%20sex%20and%20histological%20type')
58. AnnotationURLCitation(end_index=19853, start_index=19698, title='KCTD11 inhibits growth and metastasis of hepatocellular carcinoma through activating Hippo signaling | Oncotarget', type='url_citation', url='https://www.oncotarget.com/article/17145/#:~:text=problem%20in%20hepatocellular%20carcinoma,We%20found%20KCTD11%20inhibiting%20cell')
59. AnnotationURLCitation(end_index=20269, start_index=20117, title='KCTD11 inhibits growth and metastasis of hepatocellular carcinoma through activating Hippo signaling | Oncotarget', type='url_citation', url='https://www.oncotarget.com/article/17145/#:~:text=repressing%20cycle%20related%20proteins,We%20found%20the%20tumor%20suppression')
60. AnnotationURLCitation(end_index=20611, start_index=20461, title='KCTD11 inhibits growth and metastasis of hepatocellular carcinoma through activating Hippo signaling | Oncotarget', type='url_citation', url='https://www.oncotarget.com/article/17145/#:~:text=match%20at%20L107%20function%20of,suppressor%20and%20owns%20prognostic%20and')
61. AnnotationURLCitation(end_index=20852, start_index=20702, title='KCTD11 inhibits growth and metastasis of hepatocellular carcinoma through activating Hippo signaling | Oncotarget', type='url_citation', url='https://www.oncotarget.com/article/17145/#:~:text=match%20at%20L107%20function%20of,suppressor%20and%20owns%20prognostic%20and')
62. AnnotationURLCitation(end_index=21178, start_index=21026, title='KCTD11 inhibits growth and metastasis of hepatocellular carcinoma through activating Hippo signaling | Oncotarget', type='url_citation', url='https://www.oncotarget.com/article/17145/#:~:text=repressing%20cycle%20related%20proteins,We%20found%20the%20tumor%20suppression')
63. AnnotationURLCitation(end_index=21494, start_index=21342, title='KCTD11 inhibits growth and metastasis of hepatocellular carcinoma through activating Hippo signaling | Oncotarget', type='url_citation', url='https://www.oncotarget.com/article/17145/#:~:text=repressing%20cycle%20related%20proteins,We%20found%20the%20tumor%20suppression')
64. AnnotationURLCitation(end_index=22561, start_index=22390, title='RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC490020/#:~:text=Deregulation%20of%20the%20Sonic%20Hedgehog,Gli%20transcription%20factors%20to%20regulate')
65. AnnotationURLCitation(end_index=22686, start_index=22562, title='RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC490020/#:~:text=We%20have%20identified%20REN,Consistently')
66. AnnotationURLCitation(end_index=23221, start_index=23097, title='RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC490020/#:~:text=We%20have%20identified%20REN,Consistently')
67. AnnotationURLCitation(end_index=23385, start_index=23222, title='RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC490020/#:~:text=antagonizing%20the%20Gli,potential%20target%20for%20therapeutical%20intervention')
68. AnnotationURLCitation(end_index=23680, start_index=23538, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=KCASH1,58%20%2C%20%2072')
69. AnnotationURLCitation(end_index=24067, start_index=23873, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=match%20at%20L307%20KCASH1,theca%20and%20granulosa%20cell%20differentiation')
70. AnnotationURLCitation(end_index=24242, start_index=24068, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=KCASH1,theca%20and%20granulosa%20cell%20differentiation')
71. AnnotationURLCitation(end_index=24925, start_index=24727, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=Interestingly%2C%20among%20the%20genetic%20alterations,72%2C%2061%20%2C%20%2075')
72. AnnotationURLCitation(end_index=25063, start_index=24926, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=4%20%28SALL4%29%20is%20re,MB%20growth%20both%20in%20murine')
73. AnnotationURLCitation(end_index=25320, start_index=25213, title='RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC490020/#:~:text=%28arrow%29,primary%20MB')
74. AnnotationURLCitation(end_index=25482, start_index=25321, title='RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC490020/#:~:text=cell%20lines%20for%20REN%20ploidy,blood%20cells%2C%20in%20healthy%20volunteers')
75. AnnotationURLCitation(end_index=25817, start_index=25607, title='The tumor suppressor gene KCTD11 REN is regulated by Sp1 and methylation and its expression is reduced in tumors | Molecular Cancer | Full Text', type='url_citation', url='https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-9-172#:~:text=transcription%20factor%20and%20DNA%20methylation,be%20deregulated%20in%20tumor%20cells')
76. AnnotationURLCitation(end_index=26019, start_index=25818, title='The tumor suppressor gene KCTD11 REN is regulated by Sp1 and methylation and its expression is reduced in tumors | Molecular Cancer | Full Text', type='url_citation', url='https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-9-172#:~:text=whether%20methylation%20might%20regulate%20KCTD11,It%20is%20worth%20to%20note')
77. AnnotationURLCitation(end_index=26353, start_index=26184, title='The tumor suppressor gene KCTD11 REN is regulated by Sp1 and methylation and its expression is reduced in tumors | Molecular Cancer | Full Text', type='url_citation', url='https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-9-172#:~:text=We%20found%20a%20putative%20CpG,To%20evaluate')
78. AnnotationURLCitation(end_index=26528, start_index=26354, title='The tumor suppressor gene KCTD11 REN is regulated by Sp1 and methylation and its expression is reduced in tumors | Molecular Cancer | Full Text', type='url_citation', url='https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-9-172#:~:text=KCTD11%20is%20silenced%20by%20methylation,15%20and')
79. AnnotationURLCitation(end_index=26914, start_index=26713, title='The tumor suppressor gene KCTD11 REN is regulated by Sp1 and methylation and its expression is reduced in tumors | Molecular Cancer | Full Text', type='url_citation', url='https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-9-172#:~:text=whether%20methylation%20might%20regulate%20KCTD11,It%20is%20worth%20to%20note')
80. AnnotationURLCitation(end_index=27098, start_index=26915, title='The tumor suppressor gene KCTD11 REN is regulated by Sp1 and methylation and its expression is reduced in tumors | Molecular Cancer | Full Text', type='url_citation', url='https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-9-172#:~:text=clearly%20demonstrate%20a%20direct%20role,the%20region%20in')
81. AnnotationURLCitation(end_index=27508, start_index=27324, title='The tumor suppressor gene KCTD11 REN is regulated by Sp1 and methylation and its expression is reduced in tumors | Molecular Cancer | Full Text', type='url_citation', url='https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-9-172#:~:text=methylation,chromosomal%20region%2017p13%2C%20where%20KCTD11')
82. AnnotationURLCitation(end_index=27720, start_index=27509, title='The tumor suppressor gene KCTD11 REN is regulated by Sp1 and methylation and its expression is reduced in tumors | Molecular Cancer | Full Text', type='url_citation', url='https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-9-172#:~:text=methylation%20contributed%2C%20at%20least%20in,cancers%20of%20specific%20tissue%20types')
83. AnnotationURLCitation(end_index=28035, start_index=27825, title='The tumor suppressor gene KCTD11 REN is regulated by Sp1 and methylation and its expression is reduced in tumors | Molecular Cancer | Full Text', type='url_citation', url='https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-9-172#:~:text=transcription%20factor%20and%20DNA%20methylation,be%20deregulated%20in%20tumor%20cells')
84. AnnotationURLCitation(end_index=28393, start_index=28208, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=A%20significant%20reduction%20of%20KCASH1,mesenchymal%20transition')
85. AnnotationURLCitation(end_index=28713, start_index=28536, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=The%20tumor%20suppressor%20gene%20KCTD11REN,2010%3B9%3A172')
86. AnnotationURLCitation(end_index=29425, start_index=29268, title='RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC490020/#:~:text=Here%2C%20we%20describe%20the%20human,sporadic%20human%20MB%2C%20and%20its')
87. AnnotationURLCitation(end_index=29589, start_index=29426, title='RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC490020/#:~:text=antagonizing%20the%20Gli,potential%20target%20for%20therapeutical%20intervention')
88. AnnotationURLCitation(end_index=29910, start_index=29752, title='KCTD11 protein expression summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000213859-KCTD11#:~:text=Prognostic%20summary%20KCTD11%20is%20a,i%7D%20Low%20cancer%20specificity')
89. AnnotationURLCitation(end_index=30290, start_index=30113, title='KCTD11 inhibits progression of lung cancer by binding to β‐catenin to regulate the activity of the Wnt and Hippo pathways - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8500973/#:~:text=clinicopathological%20factors%20in%20patients%20with,age%2C%20sex%20and%20histological%20type')
90. AnnotationURLCitation(end_index=30610, start_index=30433, title='KCTD11 inhibits progression of lung cancer by binding to β‐catenin to regulate the activity of the Wnt and Hippo pathways - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8500973/#:~:text=clinicopathological%20factors%20in%20patients%20with,age%2C%20sex%20and%20histological%20type')
91. AnnotationURLCitation(end_index=30972, start_index=30817, title='KCTD11 inhibits growth and metastasis of hepatocellular carcinoma through activating Hippo signaling | Oncotarget', type='url_citation', url='https://www.oncotarget.com/article/17145/#:~:text=problem%20in%20hepatocellular%20carcinoma,We%20found%20KCTD11%20inhibiting%20cell')
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96. AnnotationURLCitation(end_index=33528, start_index=33414, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=lost%20in%20~30,dependent%20cancers')
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103. AnnotationURLCitation(end_index=36063, start_index=35864, title='The emerging role of the KCTD proteins in cancer | Cell Communication and Signaling | Full Text', type='url_citation', url='https://biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00737-8#:~:text=Finally%2C%20analysis%20of%20the%20COSMIC,the%20authors%20have%20observed%20that')
104. AnnotationURLCitation(end_index=37146, start_index=37032, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=lost%20in%20~30,dependent%20cancers')
105. AnnotationURLCitation(end_index=37324, start_index=37147, title='KCTD11 inhibits progression of lung cancer by binding to β‐catenin to regulate the activity of the Wnt and Hippo pathways - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8500973/#:~:text=clinicopathological%20factors%20in%20patients%20with,age%2C%20sex%20and%20histological%20type')
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111. AnnotationURLCitation(end_index=38779, start_index=38644, title='SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma | Cell Death & Differentiation', type='url_citation', url='https://www.nature.com/articles/s41418-023-01246-6#:~:text=that%20SALL4%20interacts%20with%20REN%2FKCTD11,dependent')