Malignant glioma is the most common type of primary brain tumor and represents one of the most aggressive and lethal human cancer types. Glioma recurrence is a common event; however, the relevant molecular mechanisms in this setting are not well-understood. In this study, we investigated glucose-regulated protein 94 (GRP94) expressions in human glioma and aimed to determine the roles of GRP94 expression affects cell proliferation, invasion, and regulatory signaling in human glioma U87 cells. Our results showed that GRP94 was overexpressed at both mRNA and protein levels in high-grade glioblastoma as compared with normal brain tissues. High GRP94 levels also predict shorter overall survival of glioma patients. RNAi-mediated silencing of GRP94 suppressed cellular proliferation, colony formation ability in glioma cells. Depletion of GRP94 also inhibited cell migration and invasion ability in glioma cell. Furthermore, gene microarray analysis revealed that GRP94 depletion caused the dysregulation of critical pathway, Wnt/β-catenin signaling pathway. We next demonstrated GRP94 regulates Wnt/β-catenin signaling pathway to promote the proliferation of glioblastoma cells. Conclusion, our findings establish GRP94 as progression markers and druggable targets in glioblastoma, relating their oncogenic effects to activation of the Wnt/β-catenin signaling pathway.
Keywords: GRP94; Invasion; Migration; Proliferation; Wnt/β-catenin pathway.