Document Detail


Snail1 suppresses TGF-beta-induced apoptosis and is sufficient to trigger EMT in hepatocytes.
MedLine Citation:
PMID:  20930141     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
D Lorena Franco; Jèssica Mainez; Sonia Vega; Patricia Sancho; Miguel M Murillo; Cristina A de Frutos; Gaelle Del Castillo; Cristina López-Blau; Isabel Fabregat; M Angela Nieto
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cell science     Volume:  123     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-08     Completed Date:  2011-01-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  3467-77     Citation Subset:  IM    
Affiliation:
Instituto de Neurociencias (CSIC-UMH), 03550 San Juan de Alicante, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Blotting, Western
Cell Line
Cells, Cultured
Electrophoretic Mobility Shift Assay
Epithelial-Mesenchymal Transition / genetics,  physiology*
Hepatocytes / cytology,  drug effects*,  metabolism*
Humans
Immunohistochemistry
Mice
Mice, Transgenic
Microscopy, Fluorescence
Polymerase Chain Reaction
Promoter Regions, Genetic
Rats
Transcription Factors / genetics,  metabolism*
Transforming Growth Factor beta / pharmacology*
Chemical
Reg. No./Substance:
0/Transcription Factors; 0/Transforming Growth Factor beta; 0/snail family transcription factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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