| Snail1 suppresses TGF-beta-induced apoptosis and is sufficient to trigger EMT in hepatocytes. | |
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MedLine Citation:
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PMID: 20930141 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cell science Volume: 123 ISSN: 1477-9137 ISO Abbreviation: J. Cell. Sci. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-08 Completed Date: 2011-01-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0052457 Medline TA: J Cell Sci Country: England |
Other Details:
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Languages: eng Pagination: 3467-77 Citation Subset: IM |
Affiliation:
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Instituto de Neurociencias (CSIC-UMH), 03550 San Juan de Alicante, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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