YAP Promotes Migration and Invasion of Human Glioma Cells
YAP Promotes Migration and Invasion of Human Glioma Cells
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YAP 促进人胶质瘤细胞的迁移和侵袭。
DOI：
10.1007/s12031-017-1018-6
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发表时间：
2018-02-01
影响因子：
3.1
通讯作者：
Zhou, Xiuping
中科院分区：
文献类型：
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作者：
Zhang, Yu;Xie, Peng;Zhou, Xiuping
以前，我们已经报道了，是相关蛋白（雅普）在人脑胶质瘤组织中上调，其水平与患者的预后呈正相关。然而，雅普在人脑胶质瘤高侵袭性中的作用和机制尚不清楚。本研究通过创伤愈合实验、transwell实验、活体成像等方法检测发现，雅普表达下调抑制胶质瘤细胞的迁移和侵袭，而雅普过表达促进胶质瘤细胞的迁移和侵袭。有趣的是，雅普对永生化胶质瘤细胞的上述作用在培养的原代胶质瘤细胞中重现。另外，雅普过表达后，N-cadherin和Twist两种参与肿瘤侵袭的重要蛋白的蛋白水平升高。同时，过表达雅普可显著增加F-actin水平，改变F-actin的分布，导致细胞骨架重组，在细胞运动中发挥重要作用。Twist下调可部分阻断雅普过表达对胶质瘤细胞迁移和侵袭的促进作用。总之，我们的研究结果表明，雅普有助于胶质瘤细胞的迁移和侵袭，通过调节N-钙粘蛋白和扭曲，以及细胞骨架重组。
Previously, we have reported that Yes-associated protein (YAP) is upregulated in human glioma tissues and its level is positively correlated with patient prognosis. However, the role and mechanism of YAP in the highly invasive nature of human gliomas were largely unknown. In this study, examined by wound healing assay, transwell assay, or live-imaging, we found that YAP downregulation inhibited glioma cell migration and invasion, while YAP over-expression promoted them. Interestingly, the above effect of YAP on immortalized glioma cells was recapitulated in cultured primary glioma cells. In addition, the protein level of N-cadherin and Twist, two important proteins involved in tumor invasion, increased after YAP over-expression. Meanwhile, YAP over-expression significantly increased the F-actin level and changed the distribution of F-actin, leading to cytoskeletal reorganization, which plays an important role in cell motility. Furthermore, the promotion effect of YAP over-expression on glioma cell migration and invasion was partially abolished by Twist downregulation. Taken together, our findings show that YAP contributes to glioma cell migration and invasion by regulating N-cadherin and Twist, as well as cytoskeletal reorganization.