TGFbeta-induced EMT requires focal adhesion kinase (FAK) signaling

Exp Cell Res. 2008 Jan 1;314(1):143-52. doi: 10.1016/j.yexcr.2007.09.005. Epub 2007 Sep 18.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Cadherins / metabolism
  • Cell Line
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / enzymology*
  • Focal Adhesion Protein-Tyrosine Kinases / drug effects
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / physiopathology
  • Mesoderm / cytology
  • Mesoderm / drug effects
  • Mesoderm / enzymology*
  • Mice
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / physiopathology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / physiology
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • src-Family Kinases / drug effects
  • src-Family Kinases / metabolism


  • Biomarkers, Tumor
  • Cadherins
  • Transforming Growth Factor beta
  • Focal Adhesion Protein-Tyrosine Kinases
  • src-Family Kinases