Phosphatidylinositol 4-phosphate adaptor protein 2 (FAPP2) has been recently identified as a tumor-associated regulator that is closely related to tumorigenesis. Yet, the precise role of FAPP2 in hepatocellular carcinoma (HCC) is still largely unknown. This study was designed to determine the function and molecular mechanisms of FAPP2 in HCC. Elevated expression of FAPP2 commonly occurred in the tumor tissue of HCC compared with normal controls. High expression of FAPP2 was also detected in HCC cell lines and its knockdown markedly decreased the proliferation, colony formation and invasion of HCC cells. Upregulation of FAPP2 by using a FAPP2 expression vector markedly promoted the proliferation, colony formation and invasion of HCC cells. FAPP2 was found to promote the activation of Wnt/β-catenin signaling. Importantly, inhibition of Wnt/β-catenin signaling abrogated the FAPP2 overexpression-conferred oncogenic effect in HCC cells. In addition, xenograft tumor experiments revealed that knockdown of FAPP2 significantly decreased the tumorigenicity of HCC cells in vivo. Taken together, the data of our study reported a tumor-promotion function of FAPP2 in HCC and demonstrate that knockdown of FAPP2 was capable of suppressing HCC cell proliferation and invasion through downregulation of Wnt/β-catenin signaling. This study indicated that FAPP2 might be an attractive candidate anticancer target for HCC.
Keywords: FAPP2; Hepatocellular carcinoma; Oncogene; Wnt/β-catenin.