Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma

Study ID Alternative Stable ID Type
EGAS00001003251 Other

Study Description

Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast-cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow-cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose-deprived conditions. Increased fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence ... (Show More)

Study Datasets 1 dataset.

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Dataset ID Description Technology Samples
Glioblastoma patient derived Fast/Slow cycling cancer stem cell RNA sequencing. Consists of 3 patient cell lines and 6 files
Illumina HiSeq 2500 6

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