Large-scale CRISPRi screens link metabolic stress to glioblastoma chemoresistance.

ABSTRACT:

Background

Glioblastoma (GBM) patients frequently develop resistance to temozolomide (TMZ), the standard chemotherapy. While targeting cancer metabolism shows promise, the relationship between metabolic perturbation and drug resistance remains poorly understood.

Methods

We performed high-throughput CRISPR interference screens in GBM cells to identify genes modulating TMZ sensitivity. Findings were validated using multiple GBM cell lines, patient-derived glioma stem cells, and clinical data. Molecular mechanisms were investigated through transcriptome analysis, metabolic profiling, and functional assays.

Results

We identified phosphoglycerate kinase 1 (PGK1) as a key determinant of TMZ sensitivity. Paradoxically, while PGK1 inhibition suppressed tumor growth, it enhanc

SUBMITTER: Li X 

PROVIDER: S-EPMC11887098 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature