HSP90 facilitates stemness and enhances glycolysis in glioma cells

Abstract

BackgroundGlioma is one of the most commonly occurring malignant brain cancers with high recurrence and mortality. Glioma stem cells (SCs) are a rare sub-group of glioma cells that play a critical role in tumor progression. Heat shock protein 90 (HSP90) is known to promote the stemness of glioma SCs. Here, we investigated the role of HSP90 in glioma SC metabolism, to reveal its potential as a novel therapeutic target.MethodsSelf-renewal assays were used to assess stemness. Cell migration, invasion and viability were measured using Transwell and CCK-8 assays, respectively. Tumor growth was evaluated in xenograft nude mouse models. The expression of known markers of stemness including CD44, A2B5, Oct4, Nestin, Lgr5, Sox2, CD24 were assessed by western blotting. HSP90 expression was assessed by western blotting and immunohistochemistry (IHC). Glucose consumption, lactic acid production and ATP levels were measured using commercially available kits. Extracellular acidification rates (ECAR) were measured using the Seahorse XFe/XF analyzer.ResultsHSP90 was upregulated in spheroid cells compared to parental cells. HSP90 facilitated the characteristics of SCs through enhancing self-renewal capacity, glucose consumption, lactic acid production, total ATP, ECAR and glycolysis. 2-DG, an inhibitor of glycolysis, reduced HSP90 expression and inhibited the stemness of glioma cells.ConclusionsWe show that HSP90 accelerates stemness and enhances glycolysis in glioma cells. Inhibition of glycolysis with 2DG prevented stemness. This reveals new roles for HSP90 during glioma progression and highlights this protein as a potential target for much-needed anti-glioma therapeutics.