Glutathione-s-transferase A 4 (GSTA4) suppresses tumor growth and metastasis of human hepatocellular carcinoma by targeting AKT pathway.
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.
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.
Chang Jun
CJ
Liu
Department of Hepatobiliary Surgery Hunan People's Hospital 410005, Changsha, Hunan, China.
Jin Hui
JH
Yang
Department of General Surgery, The Third Xiangya Hospital of Central South University 410013, Changsha, Hunan, China.
Fei Zhou
FZ
Huang
Department of General Surgery, The Third Xiangya Hospital of Central South University 410013, Changsha, Hunan, China.
Wan Pin
WP
Nie
Department of Hepatobiliary Surgery Hunan People's Hospital 410005, Changsha, Hunan, China.
Chu Ping
CP
Liu
Department of Hepatobiliary Surgery Hunan People's Hospital 410005, Changsha, Hunan, China.
Xian Hai
XH
Mao
Department of Hepatobiliary Surgery Hunan People's Hospital 410005, Changsha, Hunan, China.
Xin Min
XM
Yin
Department of Hepatobiliary Surgery Hunan People's Hospital 410005, Changsha, Hunan, China.
Xian Bo
XB
Shen
Department of Hepatobiliary Surgery Hunan People's Hospital 410005, Changsha, Hunan, China.
Chuang
C
Peng
Department of Hepatobiliary Surgery Hunan People's Hospital 410005, Changsha, Hunan, China.
Mei Fu
MF
Chen
Department of Hepatobiliary Surgery Hunan People's Hospital 410005, Changsha, Hunan, China.
Bo
B
Jiang
Department of General Surgery, The Third Xiangya Hospital of Central South University 410013, Changsha, Hunan, China.
Xun Yang
XY
Liu
Department of Hepatobiliary Surgery Hunan People's Hospital 410005, Changsha, Hunan, China.
Jin Shu
JS
Wu
AKT; GSTA4; hepatocellular carcinoma; metastasis