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

ABSTRACT: Extracellular signals such as TGF-? 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/EBP? as one of the most TGF-?-mediated downregulated transcription factors in human mammary epithelial cells. C/EBP? expression prevents TGF-?-driven EMT by inhibiting expression of known EMT factors. Depletion of C/EBP? is sufficient to induce mesenchymal-like morphology and molecular features, while cells that had undergone TGF-?-induced EMT reverted to an epithelial-like state upon C/EBP? re-expression. In vivo, mice injected with C/EBP?-expressing breast tumor organoids display a dramatic reduction of metastatic lesions. Collectively, our results show that C/EBP? is required for maintaining epithelial homeostasis by repressing the expression of key mesenchymal markers, thereby preventing EMT-mediated tumorigenesis. These data suggest that C/EBP? 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.

SUBMITTER: Lourenco AR 

PROVIDER: S-EPMC7005738 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature