| Literature DB >> 19597490 |
Theresa Vincent1, Etienne P A Neve, Jill R Johnson, Alexander Kukalev, Federico Rojo, Joan Albanell, Kristian Pietras, Ismo Virtanen, Lennart Philipson, Philip L Leopold, Ronald G Crystal, Antonio Garcia de Herreros, Aristidis Moustakas, Ralf F Pettersson, Jonas Fuxe.
Abstract
Epithelial-mesenchymal transition (EMT) is essential for organogenesis and is triggered during carcinoma progression to an invasive state. Transforming growth factor-beta (TGF-beta) cooperates with signalling pathways, such as Ras and Wnt, to induce EMT, but the molecular mechanisms are not clear. Here, we report that SMAD3 and SMAD4 interact and form a complex with SNAIL1, a transcriptional repressor and promoter of EMT. The SNAIL1-SMAD3/4 complex was targeted to the gene promoters of CAR, a tight-junction protein, and E-cadherin during TGF-beta-driven EMT in breast epithelial cells. SNAIL1 and SMAD3/4 acted as co-repressors of CAR, occludin, claudin-3 and E-cadherin promoters in transfected cells. Conversely, co-silencing of SNAIL1 and SMAD4 by siRNA inhibited repression of CAR and occludin during EMT. Moreover, loss of CAR and E-cadherin correlated with nuclear co-expression of SNAIL1 and SMAD3/4 in a mouse model of breast carcinoma and at the invasive fronts of human breast cancer. We propose that activation of a SNAIL1-SMAD3/4 transcriptional complex represents a mechanism of gene repression during EMT.Entities:
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Year: 2009 PMID： 19597490 PMCID： PMC3769970 DOI： 10.1038/ncb1905
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824