Abstract
The epithelial-to-mesenchymal transition (EMT) is a crucial process, occurring both during development and tumor progression, by which an epithelial cell undergoes a conversion to a mesenchymal phenotype, dissociates from initial contacts and migrates to secondary sites. We recently reported that in hepatocytes the multifunctional cytokine TGFbeta induces a full EMT characterized by (i) Snail induction, (ii) E-cadherin delocalization and down-regulation, (iii) down-regulation of the hepatocyte transcriptional factor HNF4alpha and (iv) up-regulation of mesenchymal and invasiveness markers. In particular, we showed that Snail directly causes the transcriptional down-regulation of E-cadherin and HNF4, while it is not sufficient for the up-regulation of mesenchymal and invasiveness EMT markers. In this paper, we show that in hepatocytes TGFbeta induces a Src-dependent activation of the focal adhesion protein FAK. More relevantly, we gathered results indicating that FAK signaling is required for (i) transcriptional up-regulation of mesenchymal and invasiveness markers and (ii) delocalization of membrane-bound E-cadherin. Our results provide the first evidence of FAK functional role in TGFbeta-mediated EMT in hepatocytes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biomarkers, Tumor / analysis
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Biomarkers, Tumor / metabolism
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Cadherins / metabolism
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Cell Line
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Cell Transformation, Neoplastic / drug effects
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Cell Transformation, Neoplastic / metabolism*
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Epithelial Cells / cytology
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Epithelial Cells / drug effects
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Epithelial Cells / enzymology*
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Focal Adhesion Protein-Tyrosine Kinases / drug effects
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Focal Adhesion Protein-Tyrosine Kinases / genetics
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Focal Adhesion Protein-Tyrosine Kinases / metabolism*
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Hepatocytes / cytology
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Hepatocytes / drug effects
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Hepatocytes / metabolism*
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Liver Neoplasms / enzymology
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Liver Neoplasms / physiopathology
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Mesoderm / cytology
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Mesoderm / drug effects
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Mesoderm / enzymology*
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Mice
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Neoplasm Invasiveness / genetics
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Neoplasm Invasiveness / physiopathology
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Transcriptional Activation / drug effects
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Transcriptional Activation / physiology
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Transforming Growth Factor beta / metabolism*
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Transforming Growth Factor beta / pharmacology
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Up-Regulation / drug effects
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Up-Regulation / genetics
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src-Family Kinases / drug effects
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src-Family Kinases / metabolism
Substances
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Biomarkers, Tumor
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Cadherins
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Transforming Growth Factor beta
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Focal Adhesion Protein-Tyrosine Kinases
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src-Family Kinases