摘要
TGF-beta is a potent inducer of epithelial-to-mesenchymal transition (EMT), a process involved in tumour invasion. TIF1 gamma participates in TGF-beta signalling. To understand the role of TIF1 gamma in TGF-beta signalling and its requirement for EMT, we analysed the TGF-beta 1 response of human mammary epithelial cell lines. A strong EMT increase was observed in TIF1 gamma-silenced cells after TGF-beta 1 treatment, whereas Smad4 inactivation completely blocked this process. Accordingly, the functions of several TIF1 gamma target genes can be linked to EMT, as shown by microarray analysis. As a negative regulator of Smad4, TIF1 gamma could be crucial for the regulation of TGF-beta signalling. Furthermore, TIF1 gamma binds to and represses the plasminogen activator inhibitor 1 promoter, demonstrating a direct role of TIF1 gamma in TGF-beta-dependent gene expression. This study shows the molecular relationship between TIF1 gamma and Smad4 in TGF-beta signalling and EMT.
- 出版日期2011-7