C/EBPɑ is crucial determinant of epithelial maintenance by preventing epithelial-to-mesenchymal transition.

Extracellular signals such as TGF-β can induce epithelial-to-mesenchymal transition (EMT) in cancers of epithelial origin, promoting molecular and phenotypical changes resulting in pro-metastatic characteristics. We identified C/EBPα as one of the most TGF-β-mediated downregulated transcription factors in human mammary epithelial cells. C/EBPα expression prevents TGF-β-driven EMT by inhibiting expression of known EMT factors. Depletion of C/EBPα is sufficient to induce mesenchymal-like morphology and molecular features, while cells that had undergone TGF-β-induced EMT reverted to an epithelial-like state upon C/EBPα re-expression. In vivo, mice injected with C/EBPα-expressing breast tumor organoids display a dramatic reduction of metastatic lesions. Collectively, our results show that C/EBPα is required for maintaining epithelial homeostasis by repressing the expression of key mesenchymal markers, thereby preventing EMT-mediated tumorigenesis. These data suggest that C/EBPα is a master epithelial "gatekeeper" whose expression is required to prevent unwarranted mesenchymal transition, supporting an important role for EMT in mediating breast cancer metastasis.

Citation

Ana Rita Lourenço, M Guy Roukens, Danielle Seinstra, Cynthia L Frederiks, Cornelieke E Pals, Stephin J Vervoort, Andreia S Margarido, Jacco van Rheenen, Paul J Coffer. C/EBPɑ is crucial determinant of epithelial maintenance by preventing epithelial-to-mesenchymal transition. Nature communications. 2020 Feb 07;11(1):785

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PMID: 32034145

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