WWP2 regulates proliferation of gastric cancer cells in a PTEN-dependent manner
WWP2 regulates proliferation of gastric cancer cells in a PTEN-dependent manner
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WWP2 以 PTEN 依赖性方式调节胃癌细胞的增殖
DOI：
10.1016/j.bbrc.2019.10.179
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发表时间：
2020-01-15
影响因子：
3.1
通讯作者：
Li, Jipeng
中科院分区：
文献类型：
--
作者：
Wang, Ke;Liu, Jun;Li, Jipeng
含WW结构域的E3 Ub蛋白连接酶2（WWP 2）作为PTEN的E3连接酶在肿瘤的发生发展中起重要作用。在这里，我们研究了WWP 2在胃癌（GC）中的作用。我们发现WWP 2在胃癌组织中过表达，这与胃癌患者的不良预后密切相关。利用WWP 2-shRNA慢病毒表达系统，我们建立了WWP 2稳定敲低的胃癌细胞系，发现WWP 2的敲低在体外和体内都抑制了胃癌细胞的增殖。WWP 2基因沉默可诱导PTEN蛋白水平上调和AKT磷酸化水平下调。我们通过拯救实验进一步研究了PTEN在这一调控过程中的作用，发现PTEN在WWP 2介导的GC细胞增殖调控中是必不可少的。综上所述，我们的结果表明，WWP 2通过下调PTEN促进GC细胞增殖，这可能为GC提供新的治疗靶点。(C)2019由Elsevier Inc.出版
WW domain containing E3 Ub-protein ligase 2 (WWP2) plays an important role in tumor progression as an E3 ligase of PTEN. Here, we investigated the role of WWP2 in gastric cancer ( GC). We found that WWP2 is overexpressed in GC tissues, which is closely related to poor prognosis of GC patients. Using a WWP2-shRNA lentivirus expressing system, we established WWP2 stable-knockdown GC cell lines and found that knockdown of WWP2 inhibits the proliferation of GC cells both in vitro and in vivo. Also, WWP2 silencing induced the up-regulation of PTEN protein level and down-regulation of AKT phosphorylation level. We further investigated the role of PTEN in this regulating process by performing rescue assay and found that PTEN is essential for WWP2-mediated regulation of GC cells proliferation. Taken together, our results demonstrated that WWP2 promotes proliferation of GC cells by downregulating PTEN, which may provide new therapeutic targets for GC. (C) 2019 Published by Elsevier Inc.