Downregulation of YAP inhibits proliferation, invasion and increases cisplatin sensitivity in human hepatocellular carcinoma cells.

Abstract

Yes-associated protein (YAP) serves an essential role in tumorigenesis. However, the potential role and the molecular mechanism underlying the effect of YAP on hepatocellular carcinoma (HCC) cells have not been elucidated. In the current study, it was revealed that YAP expression was increased significantly in HCC cancer tissues and its overexpression was associated with tumor differentiation. The silencing of YAP by small interferring RNA led to the inhibition of HCC cell growth, which was associated with the promotion of apoptosis. The silencing of YAP also decreased the invasive potential of HCC cells and the activity of the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway. Furthermore, silencing of YAP increased the chemosensitivity of HCC cells to cisplatin (CDDP) through inactivation of the PI3K/AKT signaling pathway. In vivo studies using PDTX model suggested a promotive role for YAP in the growth of HCC and knockdown of YAP increased the anti-tumor activity of CDDP. Taken together, these results revealed that YAP is overexpressed in HCC, and promotes proliferation, invasion and drug resistance of HCC cells. Inhibition of YAP, alone or in combination with traditional chemotherapy, may effectively combat HCC.