Abstract 4431: Musashi enhances GS3K-beta and promotes stemness-related chemoresistance in glioblastoma

Abstract

Abstract Glioblastoma multiforme (GBM), one of the deadly malignant brain tumor, and is easily to recur and develop resistance to clinical chemotherapeutics. It has been demonstrated that cisplatin treatment select for resistance but also for a more oncogenic phenotype characterized by high self-renewal and oncogenic resistance. Musashi (MSI), a neural stem cell marker, is found to be elevated in several cancer tissues and positively regulates cancer progression. In this report, we found that MSI promoted tumourigenicity and enhances drug resistance of human GBM cells in response to cisplatin, a chemodrug. We further showed that MSI could activate and interact with phosphorylated-GS3K-β, and lead to a protective effect against mitigating cisplatin-induced cell death. Knockdown of MSI effectively suppressed the phosphorylation of GS3K-β and blocked β-catenin translocating into nucleus in cisplatin-resistant GBM cells, while overexpressing MSI reversed these effects. Notably, MSI could further upregulate β-catenin-driven stemness signature, and expression of Oct-4, Nanog, and ABCG2, thereby enhanced tumorigenicity and chemoresistance of GBM cells. Moreover, the result of in vivo animal study demonstrated that knockdown MSI effectively suppressed stem-like properties, synergistically enhanced the chemotherapeutic effect, and significantly improved survival rate in GBM-transplanted immunocompromised mice. Taken together, our findings indicated that MSI-1 may provide a positive contribution to oncogenic resistance, in partly, through interplaying with GS3K-β and modulating WNT/stemness mechanism. Note: This abstract was not presented at the meeting. Citation Format: Hsiao-Yun Chen, Shih-Hwa Chiou. Musashi enhances GS3K-beta and promotes stemness-related chemoresistance in glioblastoma. [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 4431. doi:10.1158/1538-7445.AM2015-4431