2024-03-28T10:04:45Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/324292022-01-05T11:39:41Zcom_10261_133com_10261_1col_10261_386
Snail1 suppresses TGF-β-induced apoptosis and is sufficient to trigger EMT in hepatocytes
Franco, D. Lorena
Mainez, Jèssica
Vega, Sonia
Sancho, Patricia
Murillo, Miguel M.
Frutos, Cristina A. de
Castillo, Gaelle del
López-Blau, Cristina
Fabregat, Isabel
Nieto, M. Ángela
EMT
TGF-β
Apoptosis
11 páginas.
Although 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.
2011-02-16T11:43:38Z
2011-02-16T11:43:38Z
2010
artículo
Journal of Cell Science 123: 3467-3477 (2010)
0021-9533
http://hdl.handle.net/10261/32429
10.1242/jcs.068692
eng
http://dx.doi.org/10.1242/jcs.068692
openAccess
Company of Biologists