TGF-β1 signaling targets metastasis-associated protein 1, a new effector in epithelial cells

In spite of a large number of transforming growth factor beta 1 (TGF-beta 1)-regulated genes, the nature of its targets with roles in transformation continues to be poorly understood. Here, we discovered that TGF-beta 1 stimulates transcription of metastasis-associated protein 1 (MTA1), a dual master coregulator, in epithelial cells, and that MTA1 status is a determinant of TGF-beta 1-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-beta 1-stimulated mammary epithelial cells. These findings suggest that TGF-beta 1 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-beta 1 signaling in epithelial cells. Oncogene (2011) 30, 2230-2241; doi:10.1038/onc.2010.608; published online 24 January 2011