ArticleMolecular oncology2015
SNAIL1 combines competitive displacement of ASCL2 and epigenetic mechanisms to rapidly silence the EPHB3 tumor suppressor in colorectal cancer.
Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 42 citations in OpenAlex.
- Decoding the Snail transcriptional network: its role in cancer progression and therapy.Biology direct · 2026Review
- Mechanism of LPS-activated gingival fibroblasts promote the migration of gastric cancer cells via CXCL12/CXCR4-Snail2-EMT axis.In vitro cellular & developmental biology. Animal · 2026Article
- ASCL2 contributes to clinical assessments of breast cancer and mediates tumor progression via the interaction with CLDN3.Scientific reports · 2025Article
- Eph receptor tyrosine kinases are functional entry receptors for murine gammaherpesvirus 68.PLoS pathogens · 2025Article
- HPV as a Molecular Hacker: Computational Exploration of HPV-Driven Changes in Host Regulatory Networks.Viruses · 2025Article
- The β-1,4 GalT-V Interactome-Potential Therapeutic Targets and a Network of Pathways Driving Cancer and Cardiovascular and Inflammatory Diseases.International journal of molecular sciences · 2025Review
- Potential role of the Eph/ephrin system in colorectal cancer: emerging druggable molecular targets.Frontiers in oncology · 2024Review
- Article
- Construction of survival-related co-expression modules and identification of potential prognostic biomarkers of osteosarcoma using WGCNA.Annals of translational medicine · 2022Article
- Canonical TGFβ signaling induces collective invasion in colorectal carcinogenesis through a Snail1- and Zeb1-independent partial EMT.Oncogene · 2022Article
- SMAD4 mutations do not preclude epithelial-mesenchymal transition in colorectal cancer.Oncogene · 2022Article
- An Epigenetic Perspective on Intra-Tumour Heterogeneity: Novel Insights and New Challenges from Multiple Fields.Cancers · 2021Review
- Comprehensive characterization of pathological stage-related genes of papillary thyroid cancer along with survival prediction.Journal of cellular and molecular medicine · 2021Article
- Loss of the nuclear Wnt pathway effector TCF7L2 promotes migration and invasion of human colorectal cancer cells.Oncogene · 2020Article
- Yeast mismatch repair components are required for stable inheritance of gene silencing.PLoS genetics · 2020Article
- Canonical BMP Signaling Executes Epithelial-Mesenchymal Transition Downstream of SNAIL1.Cancers · 2020Article
- Article
- Snail2 induced E-cadherin suppression and metastasis in lung carcinoma facilitated by G9a and HDACs.Cell adhesion & migration · 2019Article
- G9a and histone deacetylases are crucial for Snail2-mediated E-cadherin repression and metastasis in hepatocellular carcinoma.Cancer science · 2019Article
- Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EPHB3 is a critical cellular guidance factor in the intestinal epithelium and an important tumor suppressor in colorectal cancer (CRC) whose expression is frequently lost at the adenoma-carcinoma transition when tumor cells become invasive. The molecular mechanisms underlying EPHB3 silencing are incompletely understood. Here we show that EPHB3 expression is anti-correlated with inducers of epithelial-mesenchymal transition (EMT) in primary tumors and CRC cells. In vitro, SNAIL1 and SNAIL2, but not ZEB1, repress EPHB3 reporter constructs and compete with the stem cell factor ASCL2 for binding to an E-box motif. At the endogenous EPHB3 locus, SNAIL1 triggers the displacement of ASCL2, p300 and the Wnt pathway effector TCF7L2 and engages corepressor complexes containing HDACs and the histone demethylase LSD1 to collapse active chromatin structure, resulting in rapid downregulation of EPHB3. Beyond its impact on EPHB3, SNAIL1 deregulates markers of intestinal identity and stemness and in vitro forces CRC cells to undergo EMT with altered morphology, increased motility and invasiveness. In xenotransplants, SNAIL1 expression abrogated tumor cell palisading and led to focal loss of tumor encapsulation and the appearance of areas with tumor cells displaying a migratory phenotype. These changes were accompanied by loss of EPHB3 and CDH1 expression. Intriguingly, SNAIL1-induced phenotypic changes of CRC cells are significantly impaired by sustained EPHB3 expression both in vitro and in vivo. Altogether, our results identify EPHB3 as a novel target of SNAIL1 and suggest that disabling EPHB3 signaling is an important aspect to eliminate a roadblock at the onset of EMT processes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.