ArticleCarcinogenesis2017
Fibroblast growth factor-2-mediated FGFR/Erk signaling supports maintenance of cancer stem-like cells in esophageal squamous cell carcinoma.
Article in Carcinogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 99 citations in OpenAlex.
- Role of epithelial-mesenchymal transition (EMT) in malignancies: current status and future prospects.Signal transduction and targeted therapy · 2026Review
- Repurposing the Tyrosine Kinase Inhibitors Targeting FGFR and VEGFR Pathways for Cancer Therapy: A Comprehensive Review.Cancers · 2025Review
- Targeting p-FGFR1Biomedicines · 2025Article
- Hydrogels for preventing post-endoscopic submucosal dissection stenosis in early esophageal cancer: a comprehensive literature review.Therapeutic advances in gastroenterology · 2025Review
- Chronic Kidney Disease-associated Lung Injury Is Mediated by Phosphate-induced MAPK/AKT Signaling.American journal of respiratory cell and molecular biology · 2024Article
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- Stage II oesophageal carcinoma: peril in disguise associated with cellular reprogramming and oncogenesis regulated by pseudogenes.BMC genomics · 2024Article
- Evaluation of antitumor potential of an anti-glypican-1 monoclonal antibody in preclinical lung cancer models reveals a distinct mechanism of action.Exploration of targeted anti-tumor therapy · 2024Article
- Deficiency of the histone H3K36 methyltransferase SETD2 inhibits the proliferation and migration of hepatocellular carcinoma cells.Journal of Cancer · 2024Article
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- Application of polyglycolic acid sheets and basic fibroblast growth factor to prevent esophageal stricture after endoscopic submucosal dissection in pigs.Journal of gastroenterology · 2023Article
- Phenotypic and molecular characterization of novel pulmonary adenocarcinoma cell lines established from a dog.Scientific reports · 2023Article
- SOX9 knockout decreases stemness properties in colorectal cancer cells.Journal of gastrointestinal oncology · 2023Article
- FGF-trapping hampers cancer stem-like cells in uveal melanoma.Cancer cell international · 2023Article
- Regulation of the Epithelial to Mesenchymal Transition in Osteosarcoma.Biomolecules · 2023Review
- The Molecular Characterization of Genetic Abnormalities in Esophageal Squamous Cell Carcinoma May Foster the Development of Targeted Therapies.Current oncology (Toronto, Ont.) · 2023Review
- Potential markers of cancer stem-like cells in ESCC: a review of the current knowledge.Frontiers in oncology · 2023Review
- Azelnidipine inhibits esophageal squamous cell carcinoma proliferationMolecular therapy oncolytics · 2022Article
- TNFAIP3 promotes ALDH-positive breast cancer stem cells through FGFR1/MEK/ERK pathway.Medical oncology (Northwood, London, England) · 2022Article
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
Abstract
In esophageal squamous cell carcinoma (ESCC), a subset of cells defined by high expression of CD44 and low expression of CD24 has been reported to possess characteristics of cancer stem-like cells (CSCs). Novel therapies directly targeting CSCs have the potential to improve prognosis of ESCC patients. Although fibroblast growth factor-2 (FGF-2) expression correlates with recurrence and poor survival in ESCC patients, the role of FGF-2 in regulation of ESCC CSCs has yet to be elucidated. We report that FGF-2 is significantly upregulated in CSCs and significantly increases CSC content in ESCC cell lines by inducing epithelial-mesenchymal transition (EMT). Conversely, the FGFR inhibitor, AZD4547, sharply diminishes CSCs via induction of mesenchymal-epithelial transition. Further experiments revealed that MAPK/Erk kinase (Mek)/extracellular signal-regulated kinases (Erk) pathway is crucial for FGF-2-mediated CSC regulation. Pharmacological inhibition of FGF receptor (FGFR)-mediated signaling via AZD4547 did not affect CSCs in Ras mutated cells, implying that Mek/Erk pathway, downstream of FGFR signaling, might be an important regulator of CSCs. Indeed, the Mek inhibitor, trametinib, efficiently suppressed ESCC CSCs even in the context of Ras mutation. Consistent with these findings in vitro, xenotransplantation studies demonstrated that inhibition of FGF-2-mediated FGFR/Erk signaling significantly delayed tumor growth. Taken together, these findings indicate that FGF-2 is an essential factor regulating CSCs via Mek/Erk signaling in ESCC. Additionally, inhibition of FGFR and/or Mek signaling represents a potential novel therapeutic option for targeting 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.