Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion
Central South University · Xiangya Hospital Central South University · +8 more institutions
Abstract
Abstract Glioblastoma multiforme (GBM) remains the top challenge to radiotherapy with only 25% one-year survival after diagnosis. Here, we reveal that co-enhancement of mitochondrial fatty acid oxidation (FAO) enzymes (CPT1A, CPT2 and ACAD9) and immune checkpoint CD47 is dominant in recurrent GBM patients with poor prognosis. A glycolysis-to-FAO metabolic rewiring is associated with CD47 anti-phagocytosis in radioresistant GBM cells and regrown GBM after radiation in syngeneic mice. Inhibition of FAO by CPT1 inhibitor etomoxir or CRISPR-generated CPT1A −/− , CPT2 −/− , ACAD9 −/− cells demonstrate that FAO-derived acetyl-CoA upregulates CD47 transcription via NF-κB/RelA acetylation. Blocking FAO impairs tumor…
Citation impact
- FWCI
- 18.65
- Percentile
- 100%
- References
- 99
Authors
29- NJNian JiangCorresponding
Central South University, Xiangya Hospital Central South University, University of California, Davis
- BXBowen Xie
University of California, Davis, Tsinghua University
- WXWenwu Xiao
University of California, Davis
- MFMing Fan
University of California, Davis
- SXShanxiu Xu
University of California, Davis
Topics & keywords
- CD47
- Radioresistance
- Cancer research
- Phagocytosis
- Immune system
- Biology
- Chemistry
- Immunology
Funding
- CSCentral South University
- CSChina Scholarship Council
- UOUniversity of California, DavisAwards: P30CA093373, NCI P30CA093373
- XHXiangya Hospital, Central South University
- NCNational Cancer InstituteAwards: RO1 CA213830, NCI P30CA093373, P30CA093373
- DODivision of Cancer Epidemiology and Genetics, National Cancer InstituteAwards: CA093373, CA213830, CA224900