Cbx4 Governs HIF-1α to Potentiate Angiogenesis of Hepatocellular Carcinoma by Its SUMO E3 Ligase Activity
Cbx4 Governs HIF-1α to Potentiate Angiogenesis of Hepatocellular Carcinoma by Its SUMO E3 Ligase Activity
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DOI：
10.1016/j.ccr.2013.12.008
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发表时间：
2014-01-13
期刊：
影响因子：
50.3
通讯作者：
Chen, Guo-Qiang
中科院分区：
文献类型：
--
作者：
Li, Jie;Xu, Ying;Chen, Guo-Qiang
Cbx 4是一种多梳族蛋白，也是一种SUMO E3连接酶，但其在肿瘤发生中的潜在作用仍有待探索。在这里，我们报告说，Cbx 4，而不是其他成员的Cbx家族，增强缺氧诱导的血管内皮生长因子（VEGF）的表达和血管生成在肝细胞癌（HCC）细胞通过增强HIF-1 α sumoylations在K391和K477在其两个SUMO相互作用的图案依赖性机制和增加HIF-1的转录活性。Cbx 4表达与VEGF表达、血管生成和HCC患者的总体生存率显著相关，并且在皮下和原位移植的小鼠HCC模型中也是如此。总的来说，我们的研究结果表明，Cbx 4通过控制HIF-1 α蛋白在肿瘤血管生成中起着关键作用。
Cbx4 is a polycomb group protein that is also a SUMO E3 ligase, but its potential roles in tumorigenesis remain to be explored. Here, we report that Cbx4, but not other members of the Cbx family, enhances hypoxia-induced vascular endothelial growth factor (VEGF) expression and angiogenesis in hepatocellular carcinoma (HCC) cells through enhancing HIF-1 alpha sumoylations at K391 and K477 in its two SUMO-interacting motifs-dependent mechanisms and increasing transcriptional activity of HIF-1. The Cbx4 expression is significantly correlated with VEGF expression, angiogenesis, and the overall survival of HCC patients and also in subcutaneously and orthotopically transplanted mice HCC models. Collectively, our findings demonstrate that Cbx4 plays a critical role in tumor angiogenesis by governing HIF-1 alpha protein.