biostudies-literatureDe ADepartment of Veterans Affairs | Office of Academic Affiliations, Department of Veterans AffairsBLRD VAU.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesNICHD NIH HHSNCATS NIH HHSNIDDK NIH HHSNCI NIH HHSNIH HHSNIGMS NIH HHS745-759https://www.ebi.ac.uk/biostudies/studies/S-EPMC9296259biostudies-literatureUnknown101(6)Multiple genome-wide association studies (GWAS) have linked Forkhead Box F1 (FOXF1) to Barrett's esophagus (BE). Understanding whether FOXF1 is involved in initiation of Barrett's metaplasia could allow FOXF1 to be used for risk stratification and for therapy. Two-dimensional cell cultures and three-dimensional organoid cultures and well-annotated human biopsies were used to determine the role of FOXF1 in BE pathogenesis. Multiple established esophageal squamous and BE cell lines were tested in gain- and loss-of-function studies. Initiation of a BE-like metaplastic change was evaluated by measuring characteristic cytokeratins and global gene expression profiling and by culturing organoids. Epithelial-mesenchymal transition (EMT) was evaluated by immunostaining for E-cadherin, vimentin and Laboratory investigation; a journal of technical methods and pathologyForkhead box F1 induces columnar phenotype and epithelial-to-mesenchymal transition in esophageal squamous cells to initiate Barrett's like metaplasia.PMC9296259P20 GM103418P30 GM122731I01 BX001037R01 DK107490U54 HD090216UL1 TR002366S10 OD021743BX001037P30 CA168524Bansal ADe ALiu PHuang MMathur SCChristenson LKSharma MZhang QZhou JGunewardena SfalseForkhead box F1 induces columnar phenotype and epithelial-to-mesenchymal transition in esophageal squamous cells to initiate Barrett's like metaplasia.Multiple genome-wide association studies (GWAS) have linked Forkhead Box F1 (FOXF1) to Barrett's esophagus (BE). Understanding whether FOXF1 is involved in initiation of Barrett's metaplasia could allow FOXF1 to be used for risk stratification and for therapy. Two-dimensional cell cultures and three-dimensional organoid cultures and well-annotated human biopsies were used to determine the role of FOXF1 in BE pathogenesis. Multiple established esophageal squamous and BE cell lines were tested in gain- and loss-of-function studies. Initiation of a BE-like metaplastic change was evaluated by measuring characteristic cytokeratins and global gene expression profiling and by culturing organoids. Epithelial-mesenchymal transition (EMT) was evaluated by immunostaining for E-cadherin, vimentin and 2021-01-01T00:00:00Z2021 Jun2026-05-27T22:22:24.064Z2025-04-25T18:06:58.517ZS-EPMC92962593349557510.1038/s41374-021-00534-4