Upregulation of DACT2 suppresses proliferation and enhances apoptosis of glioma cell via inactivation of YAP signaling pathway.
Upregulation of DACT2 suppresses proliferation and enhances apoptosis of glioma cell via inactivation of YAP signaling pathway.
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DACT2 上调通过 YAP 信号通路失活抑制胶质瘤细胞增殖并增强细胞凋亡
DOI：
10.1038/cddis.2017.385
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发表时间：
2017-08-10
影响因子：
9
通讯作者：
Cheng Y
中科院分区：
文献类型：
--
作者：
Tan Y;Li QM;Huang N;Cheng S;Zhao GJ;Chen H;Chen S;Tang ZH;Zhang WQ;Huang Q;Cheng Y
DACT2是Dact基因家族成员之一，具有肿瘤抑制功能。然而，它在胶质瘤中的功能在很大程度上仍不清楚。在这项研究中，我们研究了DACT2在胶质瘤患者中的作用、潜在的分子机制及其临床意义。脑胶质瘤组织中DACT2的低表达与肿瘤分级和预后密切相关。COX回归分析显示，DACT2是脑胶质瘤患者的独立预后指标。在体外，DACT2过表达抑制了胶质瘤细胞的增殖，抑制了细胞周期，增强了细胞的凋亡率，增强了对替莫唑胺的敏感性，抑制了体内肿瘤的生长。而DACT2基因的敲除则引起相反的反应。机制上，DACT2的过表达导致重要的信号分子p-yap和p-β-catenin表达上调，阻止yap移位到胞核和胞浆中的降解。本研究进一步证实DACT2通过Wnt/β-catenin信号通路抑制YAP。综上所述，这些数据表明DACT2通过失活YAP通路而具有肿瘤抑制功能，为胶质瘤的治疗提供了一个有希望的靶点。
DACT2, one of the Dact gene family members, was shown to function as a tumor suppressor. However, its function in gliomas remains largely unknown. In this study, we investigated the role of DACT2, underlying molecular mechanisms and its clinical significance in glioma patients. Downexpression of DACT2 in gliomas compared with adjacent normal brain tissues was correlated with glioma grade and poor survival. Cox regression analysis revealed that the DACT2 is an independent prognostic indicator for glioma patients. Overexpression of DACT2 in glioma cells inhibited proliferation, cell cycle and enhanced apoptosis, sensitivity to temozolomide in vitro and suppressed tumor growth in vivo. Whereas knockdown of DACT2 induce opposite reaction. Mechanistically, overexpression of DACT2 resulted in upregulation of important signaling molecules such as p-YAP and p-β-catenin, and prevent YAP translocating into nucleus and sequestering in the cytoplasm to degrade. The study further proved that DACT2 can suppress YAP through Wnt/β-catenin signaling pathway. Collectively, these data indicate that DACT2 has a tumor suppressor function via inactivation of YAP pathway, providing a promising target for the treatment of gliomas.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1126/science.1199010
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Heallen T;Zhang M;Wang J;Bonilla-Claudio M;Klysik E;Johnson RL;Martin JF
通讯作者：
Martin JF
影响因子：
7.3
作者：
Jia, Yan;Yang, Yunsheng;Brock, Malcolm V.;Zhan, Qimin;Herman, James G.;Guo, Mingzhou
通讯作者：
Guo, Mingzhou
影响因子：
2.8
作者：
Hu, Xiaobin;Xin, Yan;Zhao, Jing
通讯作者：
Zhao, Jing
影响因子：
4.8
作者：
Konsavage, Wesley M., Jr.;Kyler, Sydney L.;Yochum, Gregory S.
通讯作者：
Yochum, Gregory S.