AGK enhances angiogenesis and inhibits apoptosis via activation of the NF-κB signaling pathway in hepatocellular carcinoma.

AGK enhances angiogenesis and inhibits apoptosis via activation of the NF-κB signaling pathway in hepatocellular carcinoma.
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AGK 通过激活肝细胞癌中的 NF-κB 信号通路增强血管生成并抑制细胞凋亡

DOI:
10.18632/oncotarget.2666
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发表时间:
2014-12-15
期刊:
影响因子:
--
通讯作者:
Song L
Song L
中科院分区:
其他
文献类型:
--
作者:
Cui Y;Lin C;Wu Z;Liu A;Zhang X;Zhu J;Wu G;Wu J;Li M;Li J;Song L

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高水平的血管生成和细胞凋亡抵抗是肝细胞癌(HCC)的主要临床特征,HCC是一种在世界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。在这里,我们证明酰基甘油激酶(AGK)在 HCC 细胞系和临床组织中显着过度表达。对 245 例临床 HCC 标本的免疫组织化学分析显示,与 AGK 表达低的患者相比,AGK 表达高水平的患者的总生存期较差。此外,过表达AGK在体外显着增强血管生成并抑制细胞凋亡,在体内促进HCC细胞的致瘤性;沉默内源性 AGK 会产生相反的效果。重要的是,AGK 部分通过激活 NF-κB 信号传导增强 HCC 中的血管生成并抑制细胞凋亡。我们的研究结果提供了新的证据,表明 AGK 在促进血管生成和抵抗细胞凋亡方面发挥着重要作用,因此 AGK 可能代表 HCC 的新治疗靶点。
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.
一种产生溶血磷脂酸的新型酰基甘油激酶可调节前列腺癌细胞中与 EGFR 的串扰。
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