{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin Z"],"funding":["NCI NIH HHS"],"pagination":["1-20"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10927306"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8"],"pubmed_abstract":["Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis. Reprogramming fibroblasts toward MET via miR-200c reduces stemness and induces a senescent phenotype. This pro-tumorigenic profile in CAFs fosters carcinoma cell resistance to apoptosis, proliferation and immunosuppression, leading to primary tumor growth, metastases, and resistance to immuno-chemotherapy. Conversely, miR-200c inhibition in fibroblasts restrains tumor growth with abated oxidative stress and an anti-tumorigenic immune environment. This work determines the mechanisms by which MET in CAFs via miR-200c transcriptional enrichment with DNA demethylation triggered by oxidative stress promotes cancer progression. CAFs undergoing MET trans-differentiation and senescence coordinate heterotypic signaling that may be targeted as an anti-cancer strategy."],"journal":["Cell stress"],"pubmed_title":["MiR-200c reprograms fibroblasts to recapitulate the phenotype of CAFs in breast cancer progression."],"pmcid":["PMC10927306"],"funding_grant_id":["P30 CA056036","R37 CA234239","K08 CA175193"],"pubmed_authors":["Whitaker-Menezes D","Curry JM","Domingo-Vidal M","Caro J","Lin Z","Tuluc M","Roche ME","Diaz-Barros V","Uppal G","Martinez-Outschoorn U"],"additional_accession":[]},"is_claimable":false,"name":"MiR-200c reprograms fibroblasts to recapitulate the phenotype of CAFs in breast cancer progression.","description":"Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis. Reprogramming fibroblasts toward MET via miR-200c reduces stemness and induces a senescent phenotype. This pro-tumorigenic profile in CAFs fosters carcinoma cell resistance to apoptosis, proliferation and immunosuppression, leading to primary tumor growth, metastases, and resistance to immuno-chemotherapy. Conversely, miR-200c inhibition in fibroblasts restrains tumor growth with abated oxidative stress and an anti-tumorigenic immune environment. This work determines the mechanisms by which MET in CAFs via miR-200c transcriptional enrichment with DNA demethylation triggered by oxidative stress promotes cancer progression. CAFs undergoing MET trans-differentiation and senescence coordinate heterotypic signaling that may be targeted as an anti-cancer strategy.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024","modification":"2026-06-23T03:17:58.983Z","creation":"2026-06-23T03:09:52.315Z"},"accession":"S-EPMC10927306","cross_references":{"pubmed":["38476765"],"doi":["10.15698/cst2024.03.293"]}}