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.

磷脂酰肌醇4-磷酸衔接子蛋白2（FAPP2）最近已被确定为与肿瘤发生密切相关的肿瘤相关调节剂。但是，FAPP2在肝细胞癌（HCC）中的确切作用仍然未知。本研究旨在确定FAPP2在肝癌中的功能和分子机制。与正常对照相比，FAPP2的表达通常在肝癌的肿瘤组织中发生。在肝癌细胞系中也检测到FAPP2的高表达，其敲低显着降低了HCC细胞的增殖，集落形成和侵袭。通过使用FAPP2表达载体对FAPP2的上调显着促进了HCC细胞的增殖，集落形成和侵袭。发现FAPP2促进Wnt /β-连环蛋白信号传导的激活。重要的，对Wnt /β-catenin信号的抑制消除了HAPP细胞中FAPP2过表达赋予的致癌作用。此外，异种移植肿瘤实验表明，敲除FAPP2会显着降低体内HCC细胞的致瘤性。综上所述，我们的研究数据报道了FAPP2在肝癌中的促肿瘤作用，并证明敲除FAPP2能够通过下调Wnt /β-catenin信号传导抑制HCC细胞的增殖和侵袭。这项研究表明，FAPP2可能是HCC有吸引力的候选抗癌靶标。