PITX1 safeguards epithelial identity and restrains EMT plasticity - Nature
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AbstractEpithelial cell identity is maintained by coordinated transcriptional and epigenetic programs that preserve tissue integrity and restrain epithelial–mesenchymal transition (EMT)–driven plasticity. Through integrative transcriptomic and chromatin accessibility analyses of human mammary epithelial cells, we identify the homeobox transcription factor PITX1 as a master regulator of epithelial fate and a potent suppressor of EMT. Loss of PITX1 alone is sufficient to induce transcriptional reprogramming, cytoskeletal remodeling, and morphological shifts characteristic of EMT, comparable to those elicited by TGF-β stimulation. Conversely, restoration of PITX1 in aggressive breast cancer cells markedly reduces their migratory capacity. In patient tumors, PITX1 is enriched in epithelial compartments and EMT‑low subtypes, but downregulated in mesenchymal‑like cancers.
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