Gai3 nuclear translocation causes irradiation resistance in human glioma cells

Abstract

We have previously shown that Gai3 is elevated in human glioma, mediating Akt activation and cancer cell proliferation. Here, we imply that Gai3 could also be important for irradiation resistance. In A172 human glioma cells, Gai3 knockdown (by targeted shRNAs) or dominant-negative mutation significantly potentiated irradiation-induced cell apoptosis. Reversely, forced over-expression of wild-type or constitutively-active Gai3 inhibited irradiation-induced A172 cell apoptosis. Irradiation in A172 cells induced Gai3 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. Gai3 knockdown, depletion (using Gai3 knockout MEFs) or dominant-negative mutation potentiated irradiation-induced DNA damages. On the other hand, expression of the constitutively-active Gai3 in A172 cells inhibited DNA damage by irradiation. Together, these results indicate a novel function of Gai3 in irradiation-resistance in human glioma cells.