Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
J Environ Pathol Toxicol Oncol. 2020;39(4):309-316. doi: 10.1615/JEnvironPatholToxicolOncol.2020035441.
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.
四磷酸接头蛋白 2（FAPP2）最近被鉴定为一种与肿瘤发生密切相关的肿瘤相关调节剂。然而，FAPP2 在肝细胞癌（HCC）中的确切作用仍知之甚少。本研究旨在确定 FAPP2 在 HCC 中的功能和分子机制。与正常对照相比，FAPP2 在 HCC 肿瘤组织中普遍高表达。在 HCC 细胞系中也检测到 FAPP2 的高表达，其敲低显著降低了 HCC 细胞的增殖、集落形成和侵袭能力。使用 FAPP2 表达载体上调 FAPP2 的表达显著促进了 HCC 细胞的增殖、集落形成和侵袭。研究发现 FAPP2 促进了 Wnt/β-catenin 信号通路的激活。重要的是，抑制 Wnt/β-catenin 信号通路可消除 FAPP2 过表达赋予 HCC 细胞的致癌作用。此外，异种移植肿瘤实验表明，FAPP2 的敲低显著降低了 HCC 细胞在体内的致瘤性。总之，我们的数据揭示了 FAPP2 在 HCC 中的促肿瘤功能，并表明 FAPP2 的敲低能够通过下调 Wnt/β-catenin 信号通路抑制 HCC 细胞的增殖和侵袭。FAPP2 可能是 HCC 有吸引力的抗癌靶标。
