ArticleCancer biology & therapy2015
EGFR inhibitors prevent induction of cancer stem-like cells in esophageal squamous cell carcinoma by suppressing epithelial-mesenchymal transition.
Article in Cancer biology & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Clinical and Prognostic Implications ofDisease markers · 2020Pooled it
- KRT15 identified by scRNA-Seq and machine learning as stemness regulator and prognostic biomarker in ESCC.iScience · 2026Article
- Atlas-Guided Nanocarrier Strategies Targeting Spatial NTRK2/MAPK Signaling in EGFR-TKI-Resistant Niches of Esophageal Squamous Cell Carcinoma.Pharmaceutics · 2026Review
- PEA3 Transcription Factors, Role in Invasion, Proliferation and Radioresistance of Glioblastoma Stem Cells.Journal of cellular and molecular medicine · 2025Article
- ALDH2 dysfunction and alcohol cooperate in cancer stem cell enrichment.Carcinogenesis · 2024Article
- Article
- Potential markers of cancer stem-like cells in ESCC: a review of the current knowledge.Frontiers in oncology · 2023Review
- Correlation between amino acid metabolism and self-renewal of cancer stem cells: Perspectives in cancer therapy.World journal of stem cells · 2022Review
- Regulatory role of the transforming growth factor-β signaling pathway in the drug resistance of gastrointestinal cancers.World journal of gastrointestinal oncology · 2021Review
- Alcohol Metabolism Enriches Squamous Cell Carcinoma Cancer Stem Cells That Survive Oxidative Stress via Autophagy.Biomolecules · 2021Article
- FGFR2 maintains cancer cell differentiation via AKT signaling in esophageal squamous cell carcinoma.Cancer biology & therapy · 2021Article
- MicroRNAs as Epigenetic Determinants of Treatment Response and Potential Therapeutic Targets in Prostate Cancer.Cancers · 2021Review
- Loss of CPAP causes sustained EGFR signaling and epithelial-mesenchymal transition in oral cancer.Oncotarget · 2021Article
- CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma.Cancer cell international · 2021Article
- The Status ofInternational journal of molecular sciences · 2020Article
- Therapeutic Strategies Against Cancer Stem Cells in Esophageal Carcinomas.Frontiers in oncology · 2020Review
- Effects of cisatracurium on epithelial-to-mesenchymal transition in esophageal squamous cell carcinoma.Oncology letters · 2019Article
- Nimotuzumab Plus Paclitaxel and Cisplatin as a 1Journal of Cancer · 2019Article
- Therapeutic Strategies Targeting Cancer Stem Cells and Their Microenvironment.Frontiers in oncology · 2019Review
- From "high" ZEB1 to "low" B-cell lymphoma 2-interacting mediator of cell death (BIM)-an epithelial-mesenchymal transition (EMT)-associated drug resistance pathway elucidated.Journal of thoracic disease · 2019Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
Abstract
There exists a highly tumorigenic subset of esophageal squamous cell carcinoma (ESCC) cells defined by high expression of CD44. A novel therapy targeting these cancer stem-like cells (CSCs) is needed to improve prognosis of ESCC. CSCs of ESCC have a mesenchymal phenotype and epithelial-mesenchymal transition (EMT) is critical to enrich and maintain CSCs. EGFR, frequently overexpressed in ESCC, has pivotal roles in EMT induced by TGF-β in invasive fronts. Thus, EMT in invasive fronts of ESCC might be important for CSCs and EGFR could be a target of a novel therapy eliminating CSCs. However, effects of EGFR inhibitors on CSCs in ESCC have not been fully examined. EGFR inhibitors, erlotinib and cetuximab, significantly suppressed enrichment of CSCs via TGF-β1-mediated EMT. Importantly, EGFR inhibitors sharply suppressed ZEB1 that is essential for EMT in ESCC. Further, EGFR inhibitors activated Notch1 and Notch3, leading to squamous cell differentiation. EGFR inhibition may suppress expression of ZEB1 and induce differentiation, thereby blocking EMT-mediated enrichment of CSCs. In organotypic 3D culture, a form of human tissue engineering, tumor cells in invasive nests showed high expression of CD44. Erlotinib significantly blocked invasion into the matrix and CD44 high expressing CSCs were markedly suppressed by erlotinib in organotypic 3D culture. In conclusion, EMT is a critical process for generation of CSCs and the invasive front of ESCC, where EMT occurs, might form a CSC niche in ESCC. EGFR inhibitors could suppress EMT in invasive fronts and be one therapeutic option targeting against generation of CSCs in ESCC.
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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.