Abstract 4219: Small G protein Rac GTPases regulate the maintenance of glioblastoma stem-like cells

Abstract

Abstract Glioblastoma is the most common and aggressive malignant primary brain tumor in adults. Its invasiveness and resistance to traditional therapies make it a highly recurrent malignant disease with poor prognosis. The existence of glioblastoma stem cells (GSC) may account for its invasiveness and high recurrence, so GSCs become a suitable target for developing new treatments. Rac proteins belong to the Rho small GTPase subfamily, which major functions include regulation of cell movement, proliferation, and survival. However, most of the studies focused on Rac1 but not other Rac family proteins. To investigate whether other Rac proteins, Rac2 and Rac3, can serve as new therapeutic targets for glioblastoma, especially for glioblastoma stem cells, we examined the effects of Rac1-3 on glioblastoma cells-derived tumorspheroids (glioblastoma stem-like cells). We found that Rac1-3 are important for cell proliferation and colony formation of glioblastoma stem-like cells. We also established the zebrafish xenotransplantation model to further study the effects of Rac proteins in glioblastoma, and observed that the cells expressing control scramble short-hairpin RNA sequence induced angiogenesis in the egg yolk of the fish, while the cells expressing siRacs shrank inside the fish and did not induce angiogenesis. The overall survival rates of fishes were also higher in the fishes injected with siRac cells instead of fishes with control scramble RNA cells. Furthermore, Rac proteins also involve in STAT3 and ERK activation, and regulate the GSC marker expression such as CD133, Sox2 and HIF-2α in glioblastoma stem-like cells. In conclusion, Rac proteins can serve as the potential therapeutic targets against glioblastoma and its stem cells. Citation Format: Yun-Ju Lai, Jui-Cheng Tsai, Ying-Ting Tseng, Etty N. Benveniste. Small G protein Rac GTPases regulate the maintenance of glioblastoma stem-like cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4219. doi:10.1158/1538-7445.AM2015-4219