| Autor: |
Lourenço, Ana Rita, Roukens, M. Guy, Seinstra, Danielle, Frederiks, Cynthia L., Pals, Cornelieke E., Vervoort, Stephin J., Margarido, Andreia S., van Rheenen, Jacco, Coffer, Paul J. |
| Předmět: |
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| Zdroj: |
Nature Communications; 2/7/2020, Vol. 11 Issue 1, p1-18, 18p |
| Abstrakt: |
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. In breast cancer TGF-β regulates C/EBPα and can induce epithelial-to-mesenchymal transition (EMT). Here, the authors show that C/EBPα maintains epithelial homeostasis and prevents EMT-mediated tumorigenesis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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