FAK is involved in invasion and metastasis of hepatocellular carcinoma.
Studies have shown that focal adhesion kinase (FAK) is overexpressed in several human tumors and plays an important role in tumor progression. However, the role and underlying mechanisms of FAK in hepatocellular carcinoma (HCC) progression remains to be elucidated. In this study, we examined FAK and phosphorylated FAK Tyr397 expression in a large series of HCCs. We found that both FAK and phosphorylated FAK Tyr397 were overexpressed in HCC samples and HCC cell lines. Increased FAK and phosphorylated FAK Tyr397 expressions were correlated with tumor stage, vascular invasion and intrahepatic metastasis in HCC. Furthermore, HCC cell adhesion, migration and invasion were substantially impaired by siRNA-mediated knockdown of FAK expression, whereas cell growth, apoptosis and cell cycle distribution were not affected. In addition, depletion of FAK induced a significant reduction in expressions and activities of both MMP-2 and MMP-9. Taken together, FAK contributes to invasion and metastasis of HCC partly through regulating expressions and activations of both MMP-2 and MMP-9, suggesting FAK could be a promising therapeutic target for HCC.
Chen
Jing-Song
JS
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.
Huang
Xiao-Hui
XH
Wang
Qian
Q
Chen
Xi-Lin
XL
Fu
Xin-Hui
XH
Tan
Hao-Xiang
HX
Zhang
Long-Juan
LJ
Li
Wen
W
Bi
Jiong
J
D001483:Base Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D017931:DNA Primers; D015536:Down-Regulation; D005434:Flow Cytometry; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D017931:DNA Primers; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9