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Title

Snail1 suppresses TGF-β-induced apoptosis and is sufficient to trigger EMT in hepatocytes

AuthorsFranco, D. Lorena; Mainez, Jèssica; Vega, Sonia; Sancho, Patricia ; Murillo, Miguel M.; Frutos, Cristina A. de; Castillo, Gael del; López-Blau, Cristina; Fabregat, Isabel; Nieto, M. Ángela
KeywordsEMT
TGF-β
Apoptosis
Issue Date2010
PublisherCompany of Biologists
CitationJournal of Cell Science 123: 3467-3477 (2010)
AbstractAlthough TGF-β suppresses early stages of tumour development, it later contributes to tumour progression when cells become resistant to its suppressive effects. In addition to circumventing TGF-β-induced growth arrest and apoptosis, malignant tumour cells become capable of undergoing epithelial-to-mesenchymal transition (EMT), favouring invasion and metastasis. Therefore, defining the mechanisms that allow cancer cells to escape from the suppressive effects of TGF-β is fundamental to understand tumour progression and to design specific therapies. Here, we have examined the role of Snail1 as a suppressor of TGF-β-induced apoptosis in murine non-transformed hepatocytes, rat and human hepatocarcinoma cell lines and transgenic mice. We show that Snail1 confers resistance to TGF-β-induced cell death and that it is sufficient to induce EMT in adult hepatocytes, cells otherwise refractory to this transition upon exposure to TGF-β. Furthermore, we show that Snail1 silencing prevents EMT and restores the cell death response induced by TGF-β. As Snail1 is a known target of TGF-β signalling, our data indicate that Snail1 might transduce the tumour-promoting effects of TGF-β, namely the EMT concomitant with the resistance to cell death.
Description11 páginas.
Publisher version (URL)http://dx.doi.org/10.1242/jcs.068692
URIhttp://hdl.handle.net/10261/32429
DOI10.1242/jcs.068692
ISSN0021-9533
Appears in Collections:(IN) Artículos
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