FAK is involved in invasion and metastasis of hepatocellular carcinoma

Abstract

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.

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

“…FAK/Akt signaling is known to be activated by secreted MMP-2 and MMP-9. [30][31][32][33] Our studies showed that the phosphorylation of FAK is significantly affected only by g-CCN3 and is slightly increased by ng-CCN3 after 8 h of CCN3 treatment (Fig. 7A).…”

Bavachin Induces Apoptosis through Mitochondrial Regulated ER Stress Pathway in HepG2 Cells

“…As a matter of fact, in response to cellular stresses, Mfn2 are involved in the regulation of cell fate through a various of pathways, including the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, cytokine-cytokine receptor interaction, and focal adhesion. [54][55][56] A recent study suggested that the overexpression of Mfn2 suppressed cancer progression through inhibition of Akt signaling. 24) Furthermore, bavachin was reported to exhibit direct effect on Akt phosphorylation.…”

Identification by Differential Tissue Proteome Analysis of Talin-1 as a Novel Molecular Marker of Progression of Hepatocellular Carcinoma

“…In addition, talin-1 also functions in signal transduction in focal adhesions, as it recruits focal adhesion kinase (FAK), which in turn recruits Src and Ras to activate downstream signaling pathways [22]. It is noteworthy that FAK itself is involved in the metastasis and invasion of HCC [23]. Recently, several molecular-targeted therapies have been developed for the treatment of various malignant diseases, and the multikinase inhibitor sorafenib has shown survival benefits in patients with advanced HCC [24].…”