Gαi3 nuclear translocation causes irradiation resistance in human glioma cells

• Published in: Oncotarget 2017-05, Vol.8 (21), p.35061-35068
• Main Authors: Cai, Shang, Li, Ya, Bai, Jin-Yu, Zhang, Zhi-Qing, Wang, Yin, Qiao, Yin-Biao, Zhou, Xiao-Zhong, Yang, Bo, Tian, Ye, Cao, Cong
• Format: Article
• Language: English
• Subjects: Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - radiotherapy; Cell Line, Tumor; Cell Nucleus - metabolism; DNA Damage; DNA-Activated Protein Kinase - metabolism; Gene Expression Regulation, Neoplastic - radiation effects; Glioma - genetics; Glioma - metabolism; Glioma - radiotherapy; GTP-Binding Protein alpha Subunits, Gi-Go - genetics; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; Humans; Protein Transport; Radiation Tolerance; Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.17043

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.