Tetraspanin CD9 stabilizes gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote STAT3 activation in glioma stem cells

摘要: Glioblastoma (GBM) is the most malignant and lethal brain tumor harboring glioma stem cells (GSCs) that promote propagation therapeutic resistance. GSCs preferentially express several critical cell surface molecules regulate pro-survival signaling for maintaining cell-like phenotype. Tetraspanin CD9 has recently been reported as a GSC biomarker relevant to maintenance. However, underlying molecular mechanisms of in property remain elusive. Herein, we report stabilizes IL-6 receptor glycoprotein 130 (gp130) by preventing its ubiquitin-dependent lysosomal degradation facilitate STAT3 activation GSCs. expressed human GBM tumors. Mass spectrometry analysis identified gp130 an interacting protein GSCs, which was confirmed immunoprecipitation immunofluorescent analyses. Disrupting or shRNA significantly inhibited self-renewal promoted differentiation Moreover, disruption markedly reduced levels activating phosphorylation stabilized BMX-STAT3 Importantly, targeting potently growth vivo, while ectopic expression constitutively activated (STAT3-C) restored impaired disruption. Collectively, uncovered regulatory mechanism mediated tetraspanin maintain tumorigenic potential