Gαi3 nuclear translocation causes irradiation resistance in human glioma cells.
Gαi3 nuclear translocation causes irradiation resistance in human glioma cells.
复制标题
Gai3核易位导致人神经胶质瘤细胞产生辐射抗性
DOI：
10.18632/oncotarget.17043
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发表时间：
2017-05-23
期刊：
影响因子：
--
通讯作者：
Cao C
中科院分区：
文献类型：
--
作者：
Cai S;Li Y;Bai JY;Zhang ZQ;Wang Y;Qiao YB;Zhou XZ;Yang B;Tian Y;Cao C
我们先前已经表明，Gαi3在人脑胶质瘤中升高，介导Akt活化和癌细胞增殖。在这里，我们暗示Gαi3也可能是重要的耐辐照性。在A172人胶质瘤细胞中，Gαi3敲低（通过靶向shRNA）或显性负突变显著增强辐射诱导的细胞凋亡。抑制、强制过表达野生型或组成型活性Gαi3抑制辐射诱导的A172细胞凋亡。辐射诱导A172细胞Gαi3易位至细胞核并与局部蛋白质DNA依赖性蛋白激酶（DNA-PK）催化亚基结合。这种关联对于DNA损伤修复很重要。Gαi3敲除、耗尽（使用Gαi3敲除MEFs）或显性负突变增强辐射诱导的DNA损伤。另一方面，在A172细胞中表达组成型活性Gαi3抑制辐射引起的DNA损伤。总之，这些结果表明Gαi3在人脑胶质瘤细胞的辐射抗性中的新功能。
We have previously shown that Gαi3 is elevated in human glioma, mediating Akt activation and cancer cell proliferation. Here, we imply that Gαi3 could also be important for irradiation resistance. In A172 human glioma cells, Gαi3 knockdown (by targeted shRNAs) or dominant-negative mutation significantly potentiated irradiation-induced cell apoptosis. Reversely, forced over-expression of wild-type or constitutively-active Gαi3 inhibited irradiation-induced A172 cell apoptosis. Irradiation in A172 cells induced Gαi3 translocation to cell nuclei and association with local protein DNA-dependent protein kinase (DNA-PK) catalytic subunit. This association was important for DNA damage repair. Gαi3 knockdown, depletion (using Gαi3 knockout MEFs) or dominant-negative mutation potentiated irradiation-induced DNA damages. On the other hand, expression of the constitutively-active Gαi3 in A172 cells inhibited DNA damage by irradiation. Together, these results indicate a novel function of Gαi3 in irradiation-resistance in human glioma cells.