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Updated: Jun 7, 2026

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
Hyperglycemia promotes O-GlcNAcylation-dependent vulnerability and modulates temozolomide response in glioblastoma
Amanda Vergueiro1, Aline Menezes1, Natália Rocha1
1Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, RJ, Brazil.
Abstract:
Glioblastoma (GB) exhibits metabolic reprogramming influenced by systemic conditions such as hyperglycemia. Here, we investigated whether glycemic status modulates glycosylation pathways and therapeutic response in patient-derived GB cells. Hyperglycemia was associated with increased expression of hexosamine biosynthetic pathway (HBP) enzymes (GFAT1/2) and O-GlcNAcylation machinery (OGT/OGA), correlating with blood glucose levels and defining distinct metabolic profiles. In contrast, N-glycosylation-related enzymes showed heterogeneous regulation. Functionally, inhibition of O-GlcNAcylation reduced cell viability and enhanced sensitivity to temozolomide (TMZ), particularly in cells derived from hyperglycemic patients. These findings indicate that hyperglycemia promotes a glycosylation-dependent metabolic adaptation while creating a targetable vulnerability. Targeting O-GlcNAcylation may improve therapeutic response in hyperglycemia-associated glioblastoma.
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