ArticleThe Journal of clinical investigation2014
Hedgehog signaling regulates FOXA2 in esophageal embryogenesis and Barrett's metaplasia.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Comparative Analysis of Gastroesophageal Reflux Disease Animal Model Methods: A Data Mining of the Past Decade.Digestive diseases and sciences · 2025Pooled it
- FOXA2 in cancer: from fundamental biology to clinical translation.Frontiers in oncology · 2026Review
- The role of the fibroblast in Barrett's esophagus and esophageal adenocarcinoma.Current opinion in gastroenterology · 2024Review
- Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer.Frontiers of medicine · 2024Article
- FOXA2 activates HIF2α expression to promote tumor progression and is regulated by the E3 ubiquitin ligase VHL in renal cell carcinoma.The Journal of biological chemistry · 2024Article
- Signaling Pathways in the Pathogenesis of Barrett's Esophagus and Esophageal Adenocarcinoma.International journal of molecular sciences · 2023Review
- Construction and validation of a prognostic model based on stage-associated signature genes of head and neck squamous cell carcinoma: a bioinformatics study.Annals of translational medicine · 2022Article
- The Ephrin B2 Receptor Tyrosine Kinase Is a Regulator of Proto-oncogene MYC and Molecular Programs Central to Barrett's Neoplasia.Gastroenterology · 2022Article
- Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022Review
- Mechanisms and pathophysiology of Barrett oesophagus.Nature reviews. Gastroenterology & hepatology · 2022Review
- Modulation of hepatic stellate cells by MutaflorJournal of translational medicine · 2022Article
- A human Barrett's esophagus organoid system reveals epithelial-mesenchymal plasticity induced by acid and bile salts.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Development of an in vitro carcinogenesis model of human papillomavirus-induced cervical adenocarcinoma.Cancer science · 2022Article
- FoXA2 promotes esophageal squamous cell carcinoma progression by ZEB2 activation.World journal of surgical oncology · 2021Article
- Article
- The lncRNAsMolecular therapy. Nucleic acids · 2021Article
- GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells.Scientific reports · 2021Article
- Epithelial expression of Gata4 and Sox2 regulates specification of the squamous-columnar junction via MAPK/ERK signaling in mice.Nature communications · 2021Article
- Pediatric Patient With Concurrent Eosinophilic Esophagitis, Erosive Reflux Esophagitis, and Barrett's Esophagus.ACG case reports journal · 2020Article
- Gastrointestinal diseases among relatives of patients with esophageal atresia with or without tracheoesophageal fistula.Translational pediatrics · 2019Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
Metaplasia can result when injury reactivates latent developmental signaling pathways that determine cell phenotype. Barrett's esophagus is a squamous-to-columnar epithelial metaplasia caused by reflux esophagitis. Hedgehog (Hh) signaling is active in columnar-lined, embryonic esophagus and inactive in squamous-lined, adult esophagus. We showed previously that Hh signaling is reactivated in Barrett's metaplasia and overexpression of Sonic hedgehog (SHH) in mouse esophageal squamous epithelium leads to a columnar phenotype. Here, our objective was to identify Hh target genes involved in Barrett's pathogenesis. By microarray analysis, we found that the transcription factor Foxa2 is more highly expressed in murine embryonic esophagus compared with postnatal esophagus. Conditional activation of Shh in mouse esophageal epithelium induced FOXA2, while FOXA2 expression was reduced in Shh knockout embryos, establishing Foxa2 as an esophageal Hh target gene. Evaluation of patient samples revealed FOXA2 expression in Barrett's metaplasia, dysplasia, and adenocarcinoma but not in esophageal squamous epithelium or squamous cell carcinoma. In esophageal squamous cell lines, Hh signaling upregulated FOXA2, which induced expression of MUC2, an intestinal mucin found in Barrett's esophagus, and the MUC2-processing protein AGR2. Together, these data indicate that Hh signaling induces expression of genes that determine an intestinal phenotype in esophageal squamous epithelial cells and may contribute to the development of Barrett's metaplasia.
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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.