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

D. LORENA FRANCO, JÈSSICA MAINEZ, SONIA VEGA, PATRICIA SANCHO, MIGUEL M. MURILLO, CRISTINA A. DE FRUTOS, GAELLE DEL CASTILLO, CRISTINA LÓPEZ-BLAU, ISABEL FABREGAT AND M. ANGELA NIETO

JOURNAL OF CELL SCIENCE

COMPANY OF BIOLOGISTS LTD

Año: 2010 vol. 123 p. 3467 - 3477

0021-9533

Although TGF-b 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-b -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-b is fundamental to understand tumour progression and to design specific therapies. Here, we have examined the role of Snail1 as a suppressor of TGF-b-induced apoptosis in murine non-transformed hepatocytes, rat and human hepatocarcinoma cell lines and in transgenic mice. We show that Snail1 confers resistance to TGF-b-induced cell death and that it is sufficient to induce EMT in adult hepatocytes, cells otherwise refractory to this transition upon exposure to TGF-b. Furthermore, we show that Snail1 silencing prevents EMT and restores the cell death response induced by TGF-b. As Snail1 is a known target of TGF-b signalling, our data indicate that Snail1 might transduce the tumour-promoting effects of TGF-b namely the EMT concomitant with the resistance to cell death.