ArticleCancer research2011
A NOTCH3-mediated squamous cell differentiation program limits expansion of EMT-competent cells that express the ZEB transcription factors.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Meta-analysis of gene expression signatures defining the epithelial to mesenchymal transition during cancer progression.PloS one · 2012Pooled it
- Notch3 mediated TGF‑β1 activation enhances epithelial‑mesenchymal transition and cancer stemness in non‑small lung cancer.International journal of oncology · 2025Article
- Laminin α5: a key factor in tumor metastasis.Clinical & experimental metastasis · 2025Review
- Exploring the role of the Rab network in epithelial-to-mesenchymal transition.Bioinformatics advances · 2025Article
- Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance.Genes & diseases · 2024Review
- The p53 DNA damage response and Fanconi anemia DNA repair pathway protect against acetaldehyde-induced replication stress in esophageal keratinocytes.Cell cycle (Georgetown, Tex.) · 2023Article
- A role for age-associated alterations in esophageal epithelium in eosinophilic esophagitis-associated fibrosis.Frontiers in allergy · 2022Article
- Review
- FGFR2 maintains cancer cell differentiation via AKT signaling in esophageal squamous cell carcinoma.Cancer biology & therapy · 2021Article
- Alcohol drinking inhibits NOTCH-PAX9 signaling in esophageal squamous epithelial cells.The Journal of pathology · 2021Article
- NOTCH and Esophageal Squamous Cell Carcinoma.Advances in experimental medicine and biology · 2021Review
- Dual Effects of Non-Coding RNAs (ncRNAs) in Cancer Stem Cell Biology.International journal of molecular sciences · 2020Review
- The role of Zeb1 in the pathogenesis of morbidly adherent placenta.Molecular medicine reports · 2019Article
- Genomic characterization of early-stage esophageal squamous cell carcinoma in a Japanese population.Oncotarget · 2019Article
- The hypoxia-response pathway modulates RAS/MAPK-mediated cell fate decisions inLife science alliance · 2019Article
- B7-1 drives TGF-β stimulated pancreatic carcinoma cell migration and expression of EMT target genes.PloS one · 2019Article
- Epithelial-stromal crosstalk and fibrosis in eosinophilic esophagitis.Journal of gastroenterology · 2019Review
- IRF6 Is Directly Regulated by ZEB1 and ELF3, and Predicts a Favorable Prognosis in Gastric Cancer.Frontiers in oncology · 2019Article
- Acidic Bile Salts Induce Epithelial to Mesenchymal Transition via VEGF Signaling in Non-Neoplastic Barrett's Cells.Gastroenterology · 2019Article
- 3D Modeling of Esophageal Development using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling.Cell stem cell · 2018Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Zinc finger E-box-binding (ZEB) proteins ZEB1 and ZEB2 are transcription factors essential in TGF-β-mediated senescence, epithelial-to-mesenchymal transition (EMT), and cancer stem cell functions. ZEBs are negatively regulated by members of the miR-200 microRNA family, but precisely how tumor cells expressing ZEBs emerge during invasive growth remains unknown. Here, we report that NOTCH3-mediated signaling prevents expansion of a unique subset of ZEB-expressing cells. ZEB expression was associated with the lack of cellular capability of undergoing NOTCH3-mediated squamous differentiation in human esophageal cells. Genetic inhibition of the Notch-mediated transcriptional activity by dominant-negative Mastermind-like 1 (DNMAML1) prevented squamous differentiation and induction of Notch target genes including NOTCH3. Moreover, DNMAML1-enriched EMT-competent cells exhibited robust upregulation of ZEBs, downregulation of the miR-200 family, and enhanced anchorage-independent growth and tumor formation in nude mice. RNA interference experiments suggested the involvement of ZEBs in anchorage-independent colony formation, invasion, and TGF-β-mediated EMT. Invasive growth and impaired squamous differentiation were recapitulated upon Notch inhibition by DNMAML1 in organotypic three-dimensional culture, a form of human tissue engineering. Together, our findings indicate that NOTCH3 is a key factor limiting the expansion of ZEB-expressing cells, providing novel mechanistic insights into the role of Notch signaling in the cell fate regulation and disease progression of esophageal squamous cancers.
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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.