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Glutamine addiction promotes glucose oxidation in triple-negative breast cancer.
- Source :
-
Oncogene [Oncogene] 2022 Aug; Vol. 41 (34), pp. 4066-4078. Date of Electronic Publication: 2022 Jul 18. - Publication Year :
- 2022
-
Abstract
- Glutamine is a conditionally essential nutrient for many cancer cells, but it remains unclear how consuming glutamine in excess of growth requirements confers greater fitness to glutamine-addicted cancers. By contrasting two breast cancer subtypes with distinct glutamine dependencies, we show that glutamine-indispensable triple-negative breast cancer (TNBC) cells rely on a non-canonical glutamine-to-glutamate overflow, with glutamine carbon routed once through the TCA cycle. Importantly, this single-pass glutaminolysis increases TCA cycle fluxes and replenishes TCA cycle intermediates in TNBC cells, a process that achieves net oxidation of glucose but not glutamine. The coupling of glucose and glutamine catabolism appears hard-wired via a distinct TNBC gene expression profile biased to strip and then sequester glutamine nitrogen, but hampers the ability of TNBC cells to oxidise glucose when glutamine is limiting. Our results provide a new understanding of how metabolically rigid TNBC cells are sensitive to glutamine deprivation and a way to select vulnerable TNBC subtypes that may be responsive to metabolic-targeted therapies.<br /> (© 2022. The Author(s).)
Details
- Language :
- English
- ISSN :
- 1476-5594
- Volume :
- 41
- Issue :
- 34
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 35851845
- Full Text :
- https://doi.org/10.1038/s41388-022-02408-5