Four-phosphate adaptor-2 (FAPP2) has been recently identified as a tumor-associated regulator that is closely related to tumorigenesis. However, 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 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, our data reveal a tumor-promotion function of FAPP2 in HCC and demonstrate that knockdown of FAPP2 is capable of suppressing HCC cell proliferation and invasion through downregulation of Wnt/β-catenin signaling. FAPP2 may be an attractive candidate anticancer target for HCC.

中文翻译：

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FAPP2通过Wnt /β-Catenin信号传导促进肝癌细胞的增殖和侵袭

四磷酸衔接子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HCC细胞系中也检测到FAPP2的高表达，其敲低明显降低了HCC细胞的增殖，集落形成和侵袭。使用FAPP2表达载体上调FAPP2明显促进了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，异种移植肿瘤实验显示，FAPP2的敲低显着降低了HCC细胞的致瘤性体内。两者合计，我们的数据揭示了FAPP2在肝癌中的肿瘤促进功能，并证明FAPP2的敲低能够通过下调Wnt /β-catenin信号传导抑制HCC细胞的增殖和侵袭。FAPP2可能是HCC有吸引力的候选抗癌靶标。