The DOI matches its Crossref record; 95 of the 95 references it cites were found in a registry or an index.
Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion
Open accessAbstract
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 growth and reduces CD47 anti-phagocytosis. Etomoxir combined with anti-CD47 antibody synergizes radiation control of regrown tumors with boosted macrophage phagocytosis. These results demonstrate that enhanced fat acid metabolism promotes aggressive growth of GBM with CD47-mediated immune evasion. The FAO-CD47 axis may be targeted to improve GBM control by eliminating the radioresistant phagocytosis-proofing tumor cells in GBM radioimmunotherapy.
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Energy metabolism in health and diseases
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Metadata
- Authors
- Jiang, N., Xie, B., Xiao, W., Fan, M., Xu, S., Duan, Y., Hamsafar, Y., Evans, A. C., Huang, J., Zhou, W., Lin, X., Ye, N., Wanggou, S., Chen, W., Jing, D., Fragoso, R. C., Dugger, B. N., Wilson, P. F., Coleman, M. A., Xia, S., Li, X., Sun, L.-Q., Monjazeb, A. M., Wang, A., Murphy, W. J., Kung, H.-J., Lam, K. S., Chen, H.-W., & Li, J. J.
- Venue
- Nature Communications
- Published
- 2022-03-21
- Volume
- 13
- Issue
- 1
- Pages
- 1511-1511
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W4220872116
- Cited by
- 258
- References
- 95
- FWCI
- 27.08
- Type
- journal article
- Language
- en
- Open access
- gold
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- Jiang, N., Xie, B., Xiao, W., Fan, M., Xu, S., Duan, Y., Hamsafar, Y., Evans, A. C., Huang, J., Zhou, W., Lin, X., Ye, N., Wanggou, S., Chen, W., Jing, D., Fragoso, R. C., Dugger, B. N., Wilson, P. F., Coleman, M. A., . . . Li, J. J. (2022). Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion. Nature Communications. https://doi.org/10.1038/s41467-022-29137-3
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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