TRAF7 enhances ubiquitin-degradation of KLF4 to promote hepatocellular carcinoma progression
TRAF7 enhances ubiquitin-degradation of KLF4 to promote hepatocellular carcinoma progression
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TRAF7增强KLF4的泛素降解促进肝细胞癌进展
DOI：
10.1016/j.canlet.2019.11.012
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发表时间：
2020-01-01
期刊：
影响因子：
9.7
通讯作者：
Qu, Chunfeng
中科院分区：
文献类型：
--
作者：
He, Huan;Wu, Zhiyuan;Qu, Chunfeng
肿瘤坏死因子受体相关因子7（TRAF 7）是肿瘤坏死因子α（TNF-α）/核因子κ B（NF-κ B）途径的一种组分，是一种推定的E3-泛素连接酶。基于慢性炎症在肝细胞癌（HCC）中的重要性，我们研究了TRAF 7信号通路失调在HCC中的生物学效应和分子机制。我们的研究结果表明，TRAF 7在HCC样本中的高表达与Kruppel样因子4（KLF 4）表达和HCC患者的预后呈负相关。TRAF 7可通过泛素与KLF 4蛋白的N-末端相互作用而降解KLF 4蛋白。TRAF 7的上调促进了肝癌细胞在体内和体外的迁移和侵袭，而TRAF 7的敲低则具有相反的作用。KLF 4的恢复取消了TRAF 7诱导的运动促进作用。TRAF 7通过诱导KLF 4蛋白更新促进HCC细胞运动。
The tumor necrosis factor receptor-associated factor 7 (TRAF7) is a component of the tumor necrosis factor alpha (TNF-alpha)/nuclear factor kappa B (NF-kappa B) pathway and is a putative E3-ubiquitin ligase. Based on importance of chronic inflammation in hepatocellular carcinoma (HCC), we investigated the biological effects and the molecular mechanisms of deregulated TRAF7 signaling in HCC. Our results showed that high TRAF7 expression in HCC samples was inversely associated with Kruppel-like factor 4 (KLF4) expression and the prognosis of HCC patients. TRAF7 could degrade KLF4 protein through ubiquitin by interacting with its N-terminus. The up-regulation of TRAF7 promoted HCC cell migration and invasion in vivo and in vitro, and TRAF7 knockdown had the opposite effects. Restoration of KLF4 abrogated the motility promotion induced by TRAF7. TRAF7 promotes HCC cell motility through inducing KLF4 protein turnover.