TY - JOUR
T1 - TGFβ-induced EMT requires focal adhesion kinase (FAK) signaling
AU - Conigliaro, Alice
AU - Laudadio, Ilaria
AU - Conigliaro, Alice
AU - Steindler, Corinna
AU - Amicone, Laura
AU - Corazzari, Marco
AU - Citarella, Franca
AU - Cicchini, Carla
AU - Tripodi, Marco
AU - Fantoni, Antonio
PY - 2008
Y1 - 2008
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. © 2007 Elsevier Inc. All rights reserved.
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. © 2007 Elsevier Inc. All rights reserved.
KW - FAK; MT; Src; TGFβ; Animals; Biomarkers
KW - Neoplastic; Enzyme Activation; Epithelial Cells; Focal Adhesion Protein-Tyrosine Kinases; Hepatocytes; Liver Neoplasms; Mesoderm; Mice; Neoplasm Invasiveness; Signal Transduction; Transcriptional Activation; Transforming Growth Factor beta; Up-Regulation;
KW - Tumor; Cadherins; Cell Line; Cell Transformation
KW - FAK; MT; Src; TGFβ; Animals; Biomarkers
KW - Neoplastic; Enzyme Activation; Epithelial Cells; Focal Adhesion Protein-Tyrosine Kinases; Hepatocytes; Liver Neoplasms; Mesoderm; Mice; Neoplasm Invasiveness; Signal Transduction; Transcriptional Activation; Transforming Growth Factor beta; Up-Regulation;
KW - Tumor; Cadherins; Cell Line; Cell Transformation
UR - http://hdl.handle.net/10447/241693
M3 - Article
VL - 314
SP - 143
EP - 152
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
ER -