摘要：SummaryGlioma stem cells (GSCs) in the hypoxic niches contribute to tumor initiation, progression, and recurrence in glioblastoma (GBM). Hypoxia induces release of high-mobility group box 1 (HMGB1) from tumor cells, promoting the development of tumor. Here, we report that HMGB1 is overexpressed in human GBM specimens. Hypoxia promotes the expression and secretion of HMGB1 in GSCs. Furthermore, silencing HMGB1 results in the loss of stem cell markers and a reduction in self-renewal ability of GSCs. Additionally, HMGB1 knockdown inhibits the activation of RAGE-dependent ERK1/2 signaling pathway and arrests the cell cycle in GSCs. Consistently, FPS-ZM1, an inhibitor of RAGE, downregulates HMGB1 expression and the phosphorylation of ERK1/2, leading to a reduction in the proliferation of GSCs. In xenograft mice of GBM, HMGB1 knockdown inhibits tumor growth and promotes mouse survival. Collectively, these findings uncover a vital function for HMGB1 in regulating GSC self-renewal potential and tumorigenicity.Graphical abstractDisplay OmittedHighlights•Glioma stem cells overexpress HMGB1 in human glioblastoma•Hypoxia induces the upregulation and release of HMGB1 in glioma stem cells•HMGB1 promotes the self-renewal of glioma stem cells via RAGE•Targeting HMGB1 inhibits the tumorigenesis of glioma stem cellsBiological sciences; Cancer; Cell biology; Microenvironment; Molecular biology
