ArticleCell death and differentiation2016
DNA damage-induced ephrin-B2 reverse signaling promotes chemoresistance and drives EMT in colorectal carcinoma harboring mutant p53.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.
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Who cites it
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 99 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Systematic review of the old and new concepts in the epithelial-mesenchymal transition of colorectal cancer.World journal of gastroenterology · 2016Pooled it
- TP53 mutation at codon 179 metabolically reprograms cancer cells to promote invasion.Cancer gene therapy · 2026Article
- Association of TP53 gain-of-function mutations with early osimertinib resistance in epidermal growth factor receptor-mutant lung adenocarcinoma.ESMO open · 2026Article
- Gene Mutations and Related Molecular Events in Distant Metastasis of Cervical Cancer: A Review.International journal of medical sciences · 2026Review
- Ephrin‑B2 promotes gastric cancer growth by inhibiting apoptosis and regulating the cell cycle via the Wnt/β‑catenin signaling pathway.International journal of oncology · 2026Article
- A long non-coding RNA Leat1 mediates the hormone responsiveness of EfnB2 during male urogenital development.Communications biology · 2025Article
- c-Jun N-Terminal Kinase (JNK) Inhibitor IQ-1S as a Suppressor of Tumor Spheroid Growth.Molecules (Basel, Switzerland) · 2025Article
- Dissecting regulated cell death states and transformation mechanisms in the evolutionary trajectory of 30 cancers.iScience · 2025Article
- Long-term SiNPs exposure induced genetic instability and malignant transformation via SQSTM1/p62-mediated autophagy dysfunction in lungs.Materials today. Bio · 2025Article
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- Promising Proteolysis-Targeting Chimera for Mutant p53-R175H.ACS omega · 2024Article
- DNA-PKcs/AKT1 inhibits epithelial-mesenchymal transition during radiation-induced pulmonary fibrosis by inducing ubiquitination and degradation of Twist1.Clinical and translational medicine · 2024Article
- MSLN induced EMT, cancer stem cell traits and chemotherapy resistance of pancreatic cancer cells.Heliyon · 2024Article
- Inhibition of Ephrin B2 Reverse Signaling Abolishes Multiple Myeloma Pathogenesis.Cancer research · 2024Article
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
- Cell Death, by Any Other Name….Cells · 2024Review
- Exploring the role of cellular senescence in cancer prognosis across multiple tumor types.Frontiers in endocrinology · 2024Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- The crosstalk between ubiquitin-conjugating enzyme E2Q1 and p53 in colorectal cancer: An in vitro analysis.Medical oncology (Northwood, London, England) · 2023Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Mutation in the TP53 gene positively correlates with increased incidence of chemoresistance in different cancers. In this study, we investigated the mechanism of chemoresistance and epithelial-to-mesenchymal transition (EMT) in colorectal cancer involving the gain-of-function (GOF) mutant p53/ephrin-B2 signaling axis. Bioinformatic analysis of the NCI-60 data set and subsequent hub prediction identified EFNB2 as a possible GOF mutant p53 target gene, responsible for chemoresistance. We show that the mutant p53-NF-Y complex transcriptionally upregulates EFNB2 expression in response to DNA damage. Moreover, the acetylated form of mutant p53 protein is recruited on the EFNB2 promoter and positively regulates its expression in conjunction with coactivator p300. In vitro cell line and in vivo nude mice data show that EFNB2 silencing restores chemosensitivity in mutant p53-harboring tumors. In addition, we observed high expression of EFNB2 in patients having neoadjuvant non-responder colorectal carcinoma compared with those having responder version of the disease. In the course of deciphering the drug resistance mechanism, we also show that ephrin-B2 reverse signaling induces ABCG2 expression after drug treatment that involves JNK-c-Jun signaling in mutant p53 cells. Moreover, 5-fluorouracil-induced ephrin-B2 reverse signaling promotes tumorigenesis through the Src-ERK pathway, and drives EMT via the Src-FAK pathway. We thus conclude that targeting ephrin-B2 might enhance the therapeutic potential of DNA-damaging chemotherapeutic agents in mutant p53-bearing human tumors.
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Registered trials
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.