TY - JOUR
T1 - TGFβ-induced EMT requires focal adhesion kinase (FAK) signaling
AU - Cicchini, Carla
AU - Laudadio, Ilaria
AU - Citarella, Franca
AU - Corazzari, Marco
AU - Steindler, Corinna
AU - Conigliaro, Alice
AU - Fantoni, Antonio
AU - Amicone, Laura
AU - Tripodi, Marco
PY - 2008/1/1
Y1 - 2008/1/1
N2 - 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 TGFβ induces a full EMT characterized by (i) Snail induction, (ii) E-cadherin delocalization and down-regulation, (iii) down-regulation of the hepatocyte transcriptional factor HNF4α 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 TGFβ 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 TGFβ-mediated EMT in hepatocytes.
AB - 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 TGFβ induces a full EMT characterized by (i) Snail induction, (ii) E-cadherin delocalization and down-regulation, (iii) down-regulation of the hepatocyte transcriptional factor HNF4α 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 TGFβ 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 TGFβ-mediated EMT in hepatocytes.
KW - FAK
KW - MT
KW - Src
KW - TGFβ
UR - http://www.scopus.com/inward/record.url?scp=36549031307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36549031307&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2007.09.005
DO - 10.1016/j.yexcr.2007.09.005
M3 - Article
C2 - 17949712
AN - SCOPUS:36549031307
VL - 314
SP - 143
EP - 152
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -