Cui Yanmei, Lin Chuyong, Wu Zhiqiang, Liu Aibin, Zhang Xin, Zhu Jinrong, Wu Geyan, Wu Jueheng, Li Mengfeng, Li Jun, Song Libing
State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Oncotarget. 2014 Dec 15;5(23):12057-69. doi: 10.18632/oncotarget.2666.
High levels of angiogenesis and resistance to apoptosis are major clinical features of hepatocellular carcinoma (HCC), a lethal disease with a high incidence worldwide. However, the precise mechanisms underlying these malignant properties remain unclear. Here, we demonstrated that acylglycerol kinase (AGK) is markedly overexpressed in HCC cell lines and clinical tissues. Immunohistochemical analysis of 245 clinical HCC specimens revealed patients with high levels of AGK expression had poorer overall survival compared to patients with low AGK expression. Furthermore, overexpressing AGK significantly enhanced angiogenesis and inhibited apoptosis in vitro and promoted the tumorigenicity of HCC cells in vivo; silencing endogenous AGK had the opposite effects. Importantly, AGK enhanced angiogenesis and inhibited apoptosis in HCC in part via activation of NF-κB signaling. Our findings provide new evidence that AGK plays an important role in promoting angiogenesis and providing resistance to apoptosis, thus AGK may represent a novel therapeutic target for HCC.
高水平的血管生成和抗凋亡能力是肝细胞癌（HCC）的主要临床特征，HCC是一种在全球范围内发病率很高的致命疾病。然而，这些恶性特性背后的确切机制仍不清楚。在此，我们证明了酰基甘油激酶（AGK）在肝癌细胞系和临床组织中明显过表达。对245例临床肝癌标本的免疫组化分析显示，与AGK低表达患者相比，AGK高表达患者的总生存期更差。此外，过表达AGK在体外显著增强血管生成并抑制凋亡，在体内促进肝癌细胞的致瘤性；沉默内源性AGK则产生相反的效果。重要的是，AGK部分通过激活NF-κB信号通路增强肝癌中的血管生成并抑制凋亡。我们的研究结果提供了新的证据，表明AGK在促进血管生成和提供抗凋亡能力方面发挥重要作用，因此AGK可能代表肝癌的一个新的治疗靶点。
