ArticleCell death and differentiation2022
Epithelial de-differentiation triggered by co-ordinate epigenetic inactivation of the EHF and CDX1 transcription factors drives colorectal cancer progression.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- ETS Homologous Factor (EHF) and Gamma Linolenic Acid (GLA): novel strategies for early diagnosis and treatment of endometriosis.Functional & integrative genomics · 2026Article
- Molecular mechanisms of KMT2C alterations in gastrointestinal cancers: enhancer network destabilization, lineage plasticity, and clinical translation.Frontiers in immunology · 2026Review
- EHF as a key regulator mediating cell migration and may contribute to tumor immune infiltration and progression in human endometrial cancer.BMC cancer · 2025Article
- Multi-omic characterization of consensus molecular subtype 1 (CMS1) colorectal cancer with dampened immune response improves precision medicine.Molecular oncology · 2025Article
- Model systems and unique biological features of high and low-grade colorectal cancer (CRC) revealed by xenografting 84 human CRC cell lines.Communications biology · 2025Article
- CDX1 and CDX2 suppress colon cancer stemness by inhibiting β-catenin-facilitated formation of Pol II-DSIF-PAF1C complex.Cell death & disease · 2025Article
- Notch2 Inhibition and Kidney Cyst Growth in Autosomal Dominant Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2025Article
- CDX1 improves nicotine induced cardiac fibroblasts activation and cardiomyocyte hypertrophy by alleviating autophagic flux impairment through modulation of LAPTM4B.Scientific reports · 2025Article
- Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients.Nature communications · 2025Article
- Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients.medRxiv : the preprint server for health sciences · 2025Article
- GPA33 expression in colorectal cancer can be induced by WNT inhibition and targeted by cellular therapy.Oncogene · 2025Article
- Nonlinear DNA methylation trajectories in aging male mice.Nature communications · 2024Article
- The androgen receptor interacts with GATA3 to transcriptionally regulate a luminal epithelial cell phenotype in breast cancer.Genome biology · 2024Article
- Genomic and transcriptomic profiling of hepatocellular carcinoma reveals a rare molecular subtype.Discover oncology · 2024Article
- Heme Oxygenase-1 and Its Role in Colorectal Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- Multi-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells.Chemico-biological interactions · 2023Article
Corrections and comments
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Authors and funding
32 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancers (CRCs) often display histological features indicative of aberrant differentiation but the molecular underpinnings of this trait and whether it directly drives disease progression is unclear. Here, we identify co-ordinate epigenetic inactivation of two epithelial-specific transcription factors, EHF and CDX1, as a mechanism driving differentiation loss in CRCs. Re-expression of EHF and CDX1 in poorly-differentiated CRC cells induced extensive chromatin remodelling, transcriptional re-programming, and differentiation along the enterocytic lineage, leading to reduced growth and metastasis. Strikingly, EHF and CDX1 were also able to reprogramme non-colonic epithelial cells to express colonic differentiation markers. By contrast, inactivation of EHF and CDX1 in well-differentiated CRC cells triggered tumour de-differentiation. Mechanistically, we demonstrate that EHF physically interacts with CDX1 via its PNT domain, and that these transcription factors co-operatively drive transcription of the colonic differentiation marker, VIL1. Compound genetic deletion of Ehf and Cdx1 in the mouse colon disrupted normal colonic differentiation and significantly enhanced colorectal tumour progression. These findings thus reveal a novel mechanism driving epithelial de-differentiation and tumour progression in CRC.
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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.