ArticleProceedings of the National Academy of Sciences of the United States of America2014
Silencing of the EPHB3 tumor-suppressor gene in human colorectal cancer through decommissioning of a transcriptional enhancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Emerging Protein Targets in Triple-Negative Breast Cancer: Beyond Conventional Therapy.Cancers · 2026Review
- Eph receptor tyrosine kinases are functional entry receptors for murine gammaherpesvirus 68.PLoS pathogens · 2025Article
- Potential role of the Eph/ephrin system in colorectal cancer: emerging druggable molecular targets.Frontiers in oncology · 2024Review
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- Construction of survival-related co-expression modules and identification of potential prognostic biomarkers of osteosarcoma using WGCNA.Annals of translational medicine · 2022Article
- SMAD4 mutations do not preclude epithelial-mesenchymal transition in colorectal cancer.Oncogene · 2022Article
- Comprehensive characterization of pathological stage-related genes of papillary thyroid cancer along with survival prediction.Journal of cellular and molecular medicine · 2021Article
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- A Molecular Test for Quantifying Functional Notch Signaling Pathway Activity in Human Cancer.Cancers · 2020Article
- Loss of mismatch repair signaling impairs the WNT-bone morphogenetic protein crosstalk and the colonic homeostasis.Journal of molecular cell biology · 2020Article
- Loss of the nuclear Wnt pathway effector TCF7L2 promotes migration and invasion of human colorectal cancer cells.Oncogene · 2020Article
- Article
- Receptor Tyrosine Kinase EphB3: a Prognostic Indicator in Colorectal Carcinoma.Pathology oncology research : POR · 2020Article
- Identification of Eph receptor signaling as a regulator of autophagy and a therapeutic target in colorectal carcinoma.Molecular oncology · 2019Article
- Article
- Epigenetic Control of the Notch and Eph Signaling Pathways by the Prion Protein: Implications for Prion Diseases.Molecular neurobiology · 2019Article
- Sonic hedgehog pathway activation is associated with cetuximab resistance and EPHB3 receptor induction in colorectal cancer.Theranostics · 2019Article
- Role of EphB3 Receptor in Mediating Head and Neck Tumor Growth, Cell Migration, and Response to PI3K Inhibitor.Molecular cancer therapeutics · 2018Article
- Article
- EphA10 and EphB3 are prognostic markers in gallbladder squamous cell/adenosquamous carcinomas and adenocarcinomas.International journal of clinical and experimental pathology · 2018Article
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protein tyrosine kinase Ephrin type-B receptor 3 (EPHB3) counteracts tumor-cell dissemination by regulating intercellular adhesion and repulsion and acts as tumor/invasion suppressor in colorectal cancer. This protective mechanism frequently collapses at the adenoma-carcinoma transition due to EPHB3 transcriptional silencing. Here, we identify a transcriptional enhancer at the EPHB3 gene that integrates input from the intestinal stem-cell regulator achaete-scute family basic helix-loop-helix transcription factor 2 (ASCL2), Wnt/β-catenin, MAP kinase, and Notch signaling. EPHB3 enhancer activity is highly variable in colorectal carcinoma cells and precisely reflects EPHB3 expression states, suggesting that enhancer dysfunction underlies EPHB3 silencing. Interestingly, low Notch activity parallels reduced EPHB3 expression in colorectal carcinoma cell lines and poorly differentiated tumor-tissue specimens. Restoring Notch activity reestablished enhancer function and EPHB3 expression. Although essential for intestinal stem-cell maintenance and adenoma formation, Notch activity seems dispensable in colorectal carcinomas. Notch activation even promoted growth arrest and apoptosis of colorectal carcinoma cells, attenuated their self-renewal capacity in vitro, and blocked tumor growth in vivo. Higher levels of Notch activity also correlated with longer disease-free survival of colorectal cancer patients. In summary, our results uncover enhancer decommissioning as a mechanism for transcriptional silencing of the EPHB3 tumor suppressor and argue for an antitumorigenic function of Notch signaling in advanced colorectal cancer.
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