Format

Send to

Choose Destination
Exp Cell Res. 2008 Jan 1;314(1):143-52. Epub 2007 Sep 18.

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

Author information

1
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Rome, Italy.

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.

PMID:
17949712
DOI:
10.1016/j.yexcr.2007.09.005
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center