Mst1 regulates glioma cell proliferation via the AKT/mTOR signaling pathway
Mst1 regulates glioma cell proliferation via the AKT/mTOR signaling pathway
复制标题
Mst1 通过 AKT/mTOR 信号通路调节胶质瘤细胞增殖
DOI：
10.1007/s11060-014-1654-4
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发表时间：
2015-01-01
影响因子：
3.9
通讯作者：
Zhou, Xiuping
中科院分区：
文献类型：
--
作者：
Chao, Yuewen;Wang, Yan;Zhou, Xiuping
哺乳动物不育20-样蛋白1(Mst1)是河马途径上游丝氨酸/苏氨酸特异的蛋白激酶，通过调节细胞增殖和存活，在哺乳动物的肿瘤抑制和器官大小调节中发挥重要作用。然而，它是否参与了恶性胶质瘤的发病机制仍然知之甚少。因此，本研究旨在探讨Mst1对恶性胶质瘤细胞增殖和凋亡的影响及其机制。EDU掺入法和CCK-8比色法检测细胞增殖和生长情况。用流式细胞仪检测细胞的凋亡率。我们发现Mst1的下调促进了胶质瘤细胞的增殖和生长，但抑制了细胞的凋亡。与此一致的是，Mst1的过表达抑制了胶质瘤细胞的增殖和生长。有趣的是，Mst1不影响河马途径的关键下游分子YAP1的磷酸化。然而，在胶质瘤细胞中，Mst1被发现与AKT结合，并负向调节AKT和mTOR活性。最后，下调AKT1可部分消除Mst1下调所引起的细胞增殖率的增加。同时，AKT1的过表达可部分缓解Mst1过表达对胶质瘤细胞生长的抑制作用。综上所述，这些发现提示Mst1通过AKT/mTOR信号通路调节胶质瘤细胞的增殖。
Mammalian sterile 20-like 1 (Mst1), an upstream serine/threonine-specific protein kinase of the Hippo pathway, is reported to play important roles in tumor suppression and organ size regulation in mammals via regulating cell proliferation and survival. However, whether it is involved in the pathogenesis of malignant gliomas remains poorly understood. Therefore, in the present work, we examined the effect and mechanism of Mst1 on the proliferation and apoptosis of malignant glioma cells. The cell proliferation and growth of glioma cells were examined by EdU incorporation and CCK-8 assay. In addition, the cell apoptosis was assessed by flow cytometry. We found that down-regulation of Mst1 promoted glioma cell proliferation and growth, but inhibited the cell apoptosis. Consistent with this, over-expression of Mst1 inhibited glioma cell proliferation and growth. Interestingly, Mst1 did not affect the phosphorylation of YAP1, the key downstream molecule of Hippo pathway. However, Mst1 was found to bind to AKT in glioma cell and negatively regulated AKT and mTOR activity. Finally, the increased cell proliferation rate induced by Mst1 down-regulation was partially abolished by down-regulation of AKT1. Meanwhile, glioma cell growth inhibition induced by Mst1 over-expression was partially rescued by over-expression of AKT1. Taken together, these findings suggest that Mst1 regulates proliferation of glioma cells via AKT/mTOR signaling pathway.