TGFbeta-induced EMT requires focal adhesion kinase (FAK) signaling.
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.
Cicchini
Carla
C
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Rome, Italy.
Laudadio
Ilaria
I
Citarella
Franca
F
Corazzari
Marco
M
Steindler
Corinna
C
Conigliaro
Alice
A
Fantoni
Antonio
A
Amicone
Laura
L
Tripodi
Marco
M
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms / Q000201:enzymology / Q000503:physiopathology; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D019061:src-Family Kinases / Q000187:drug effects / Q000378:metabolism
D014408:Biomarkers, Tumor; D015820:Cadherins; D016212:Transforming Growth Factor beta; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases