期刊
EMBO JOURNAL
卷 37, 期 23, 页码 -出版社
WILEY
DOI: 10.15252/embj.201798772
关键词
brain cancer; cancer stem cells; glioblastoma; metabolism; slow-cycling cells
资金
- American Brain Tumor Association Basic Research Fellowship Grant
- Tenovus Cancer Care [TIG2015/L19]
- Cancer Research UK Cardiff Centre
- Preston A. Wells, Jr. Endowment [00107592, 1K08CA199224-01A1]
- American Cancer Society Research Scholar Grant [RSG-13-031-01-DDC]
- Preston A. Wells, Jr. Brain Tumor Research Fund
- NINDS [R24 NS086554-01]
- American Cancer Society Chris DiMarco Institutional Research Grant
- Accelerate Brain Cancer Cure
- American Brain Tumor Association Research Grant [DG1800014]
- Robert P. Apkarian Integrated Electron Microscopy Core (RPAIEMC)
- Emory College of Arts and Sciences
- Emory University School of Medicine
- NIH [1S10OD020026]
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. 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 of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7-related metabolic pathways is a viable therapeutic strategy.
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