Abstract
In spite of a large number of transforming growth factor Β1 (TGF-Β1)-regulated genes, the nature of its targets with roles in transformation continues to be poorly understood. Here, we discovered that TGF-Β1 stimulates transcription of metastasis-associated protein 1 (MTA1), a dual master coregulator, in epithelial cells, and that MTA1 status is a determinant of TGF-Β1-induced epithelial-to-mesenchymal transition (EMT) phenotypes. In addition, we found that MTA1/polymerase II/activator protein-1 (AP-1) co-activator complex interacts with the FosB-gene chromatin and stimulates its transcription, and FosB in turn, utilizes FosB/histone deacetylase 2 complex to repress E-cadherin expression in TGF-Β1-stimulated mammary epithelial cells. These findings suggest that TGF-Β1 regulates the components of EMT via stimulating the expression of MTA1, which in turn, induces FosB to repress E-cadherin expression and thus, revealed an inherent function of MTA1 as a target and effector of TGF-Β1 signaling in epithelial cells.
Original language | English (US) |
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Pages (from-to) | 2230-2241 |
Number of pages | 12 |
Journal | Oncogene |
Volume | 30 |
Issue number | 19 |
DOIs | |
State | Published - May 12 2011 |
Externally published | Yes |
Keywords
- FosB
- MTA1
- TGF-β1 signaling
- epithelial-to-mesenchymal transition
- target gene transcription
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research