Liu Chang Jun, Yang Jin Hui, Huang Fei Zhou, Nie Wan Pin, Liu Chu Ping, Mao Xian Hai, Yin Xin Min, Shen Xian Bo, Peng Chuang, Chen Mei Fu, Jiang Bo, Liu Xun Yang, Wu Jin Shu
Department of General Surgery, The Third Xiangya Hospital of Central South University410013, Changsha, Hunan, China; Department of Hepatobiliary Surgery Hunan People's Hospital410005, Changsha, Hunan, China.
Department of Hepatobiliary Surgery Hunan People's Hospital 410005, Changsha, Hunan, China.
Am J Transl Res. 2017 Feb 15;9(2):301-315. eCollection 2017.
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies of cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Up-regulation of glutathione-s-transferase A 4 (GSTA4) is associated with poor prognosis of HCC, but its functional mechanism in HCC remains unclear. In this study, we investigated the roles of GSTA4 in tumor growth and metastasis of HCC and found that GSTA4 was frequently up-regulated in HCC tissues. Through gain- and loss-of-function studies, GSTA4 was demonstrated to significantly regulate cell proliferation, migration, and invasion in vitro. Furthermore, GSTA4 overexpressing significantly promoted the tumorigenicity and metastasis of HCC cells in nude mice models bearing human HCC, whereas silencing endogenous GSTA4 caused an opposite outcome. Moreover, we demonstrated that GSTA4 enhanced HCC aggressiveness by activating protein kinase B (AKT) signaling. In multivariate analysis, our results GSTA4 overexpression promotes the progression of hepatocellular carcinoma and might represent a novel therapeutic target for its treatment.
肝细胞癌（HCC）是最致命的恶性肿瘤之一，由于缺乏有效的治疗靶点，其预后仍然很差。谷胱甘肽 - S - 转移酶A4（GSTA4）的上调与HCC的不良预后相关，但其在HCC中的功能机制仍不清楚。在本研究中，我们研究了GSTA4在HCC肿瘤生长和转移中的作用，发现GSTA4在HCC组织中经常上调。通过功能获得和功能丧失研究，证明GSTA4在体外显著调节细胞增殖、迁移和侵袭。此外，在携带人HCC的裸鼠模型中，过表达GSTA4显著促进了HCC细胞的致瘤性和转移，而沉默内源性GSTA4则产生相反的结果。此外，我们证明GSTA4通过激活蛋白激酶B（AKT）信号增强了HCC的侵袭性。在多变量分析中，我们的结果表明GSTA4过表达促进肝细胞癌的进展，可能代表其治疗的新靶点。
