Antagonistic regulation of EMT by TIF1γ and Smad4 in mammary epithelial cells.
EMBO Rep
; 12(7): 665-72, 2011 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-21597466
ABSTRACT
TGF-ß is a potent inducer of epithelial-to-mesenchymal transition (EMT), a process involved in tumour invasion. TIF1γ participates in TGF-ß signalling. To understand the role of TIF1γ in TGF-ß signalling and its requirement for EMT, we analysed the TGF-ß1 response of human mammary epithelial cell lines. A strong EMT increase was observed in TIF1γ-silenced cells after TGF-ß1 treatment, whereas Smad4 inactivation completely blocked this process. Accordingly, the functions of several TIF1γ target genes can be linked to EMT, as shown by microarray analysis. As a negative regulator of Smad4, TIF1γ could be crucial for the regulation of TGF-ß signalling. Furthermore, TIF1γ binds to and represses the plasminogen activator inhibitor 1 promoter, demonstrating a direct role of TIF1γ in TGF-ß-dependent gene expression. This study shows the molecular relationship between TIF1γ and Smad4 in TGF-ß signalling and EMT.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Glândulas Mamárias Humanas
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Células Epiteliais
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Proteína Smad4
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article