Hypoxia-induced S100A10 promotes glioblastoma malignancy and chemoresistance by activating PI3K-AKT signaling pathway

Abstract

Glioblastoma (GBM) is the most frequent and lethal subtype of glioma that leads to unsatisfactory clinical outcomes. Hypoxia-induced chemoresistance exacerbates therapy. S100 calcium-binding protein A10 (S100A10) plays a crucial role in the oncogenesis of multiple human tumors. However, its role in to hypoxia-driven GBM progression and chemoresistance remains unclear. S100A10 was identified as a key gene because of its significant upregulation in GBM, hypoxia-treated GBM cells and temozolomide (TMZ)-resistant GBM cells. Public datasets, quantitative PCR (qPCR) and Western blot were performed to determine the levels of S100A10 in gliomas and cell lines. The clinical relevance, prognostic significance, and functional enrichment of S100A10 were fully assessed using open resources from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). CCK8, 5-ethynyl-2’-deoxyuridine (EdU) incorporation, colony formation, annexin V staining, and flow cytometry assays were used to measure the proliferation, cell cycle, and apoptosis of GBM cells in vitro. Glycolysis potential was examined by determining lactate and pyruvate production. The interaction between hypoxia and S100A10 was assessed by qPCR and Western blot. Our study suggests that hypoxia-induced S100A10 expression facilitates proliferation and glycolysis and inhibits apoptosis by regulating the PI3K-AKT signaling pathway, which enhances TMZ resistance in GBM cells.