Glutamine addiction promotes glucose oxidation in triple-negative breast cancer.

Autor: Quek LE; School of Mathematics and Statistics, The University of Sydney, Camperdown, NSW, Australia. lake-ee.quek@sydney.edu.au., van Geldermalsen M; Origins of Cancer Program, Centenary Institute, The University of Sydney, Camperdown, NSW, Australia.; Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia., Guan YF; School of Medical Sciences and School of Clinical Medicine, UNSW Sydney, Kensington, NSW, Australia., Wahi K; School of Medical Sciences and School of Clinical Medicine, UNSW Sydney, Kensington, NSW, Australia., Mayoh C; Children's Cancer Institute, Lowy Cancer Centre, UNSW Sydney, Kensington, NSW, Australia.; School of Women's and Children's Health, UNSW Sydney, Kensington, NSW, Australia., Balaban S; School of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia., Pang A; School of Medical Sciences and School of Clinical Medicine, UNSW Sydney, Kensington, NSW, Australia., Wang Q; School of Medical Sciences and School of Clinical Medicine, UNSW Sydney, Kensington, NSW, Australia., Cowley MJ; Children's Cancer Institute, Lowy Cancer Centre, UNSW Sydney, Kensington, NSW, Australia.; School of Women's and Children's Health, UNSW Sydney, Kensington, NSW, Australia., Brown KK; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.; Department of Biochemistry and Pharmacology, The University of Melbourne, Melbourne, VIC, Australia., Turner N; Department of Pharmacology, School of Medical Sciences, UNSW Sydney, Kensington, NSW, Australia., Hoy AJ; School of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia., Holst J; School of Medical Sciences and School of Clinical Medicine, UNSW Sydney, Kensington, NSW, Australia. j.holst@unsw.edu.au.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2022 Aug; Vol. 41 (34), pp. 4066-4078. Date of Electronic Publication: 2022 Jul 18.
DOI: 10.1038/s41388-022-02408-5
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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