β-catenin-mediated YAP signaling promotes human glioma growth.
β-catenin-mediated YAP signaling promotes human glioma growth.
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β-连环蛋白介导的 YAP 信号促进人神经胶质瘤生长
DOI：
10.1186/s13046-017-0606-1
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发表时间：
2017-09-29
期刊：
影响因子：
--
通讯作者：
Zhou X
中科院分区：
文献类型：
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作者：
Wang Y;Pan P;Wang Z;Zhang Y;Xie P;Geng D;Jiang Y;Yu R;Zhou X
Hippo/YAP通路在发育、生长和器官发生中起重要作用，该通路的失调会导致肿瘤进展。我们和其他人发现YAP在人类胶质瘤中上调，并与患者预后较差相关。然而，YAP在胶质瘤进展中的作用和机制在很大程度上是未知的。采用定量聚合酶链反应（qPCR）和免疫印迹法检测YAP在胶质瘤组织中的表达。通过细胞生长试验和颅内胶质瘤模型研究YAP对胶质瘤进展的影响。采用免疫印迹、免疫荧光和RT-PCR检测YAP对β-catenin蛋白水平、亚细胞定位和转录活性的影响。首先，YAP的下调抑制了胶质瘤细胞的体外增殖和体内肿瘤的生长。此外，YAP通过调节GSK3β的活性来调节β-catenin的蛋白水平、亚细胞定位和转录活性。最后，β-catenin部分介导YAP对胶质瘤细胞增殖的影响。我们的研究结果表明，YAP通过增强Wnt/β-catenin信号传导促进人类胶质瘤的生长。此外，本研究提供了Hippo/YAP与Wnt/β-catenin通路之间新的串音机制，为人类胶质瘤治疗提供了新的策略。本文的在线版本（10.1186/s13046-017-0606-1）包含补充资料，仅供授权用户使用。
Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression.We and others find that YAP is up-regulated in human gliomas and associated with worse prognosis of patients. However, the role and mechanism of YAP in glioma progression is largely unknown. The expression of YAP in glioma tissues was detected by quantitative polymerase chain reaction (qPCR) and immunoblotting. The effect of YAP on glioma progression was examined using cell growth assays and intracranial glioma model. The effect of YAP on β-catenin protein level, subcellular location and transcription activity was examined by immunoblotting, immunofluorescence and RT-PCR. Firstly, knockdown of YAP inhibited glioma cell proliferation in vitro and tumor growth in vivo. In addition, YAP modulated the protein level, subcellular location and transcription activity of β-catenin via regulating the activity of GSK3β. Lastly, β-catenin partially mediated the effect of YAP on glioma cell proliferation. Our findings identify that YAP promotes human glioma growth through enhancing Wnt/β-catenin signaling. In addition, this study provides a new crosstalk mechanism between Hippo/YAP and Wnt/β-catenin pathways, which suggests a new strategy for human glioma treatment. The online version of this article (10.1186/s13046-017-0606-1) contains supplementary material, which is available to authorized users.