Reactive metabolite production is a targetable liability of glycolytic metabolism in lung cancer
Name
s41467-019-13419-4.pdf
Description
Published version
Size
1.15 MB
Format
Adobe PDF
Checksum (MD5)
13d69ea539e6b6000672c57a16f046ec
Author(s)
Luengo, Alba
Abbott, Keene L.
Davidson, Shawn M.
Hosios, Aaron M.
Chan, Sze Ham
Freinkman, Elizaveta
Lewis, Caroline A.
Vander Heiden, Matthew G.
Date Issued
December 2019
Journal
Nature communications
Publisher
Springer Science and Business Media LLC
Citation
Luengo, Alba et al. "Reactive metabolite production is a targetable liability of glycolytic metabolism in lung cancer." Nature communications 10 (2019): s41467-019-13419 © 2019 The Author(s)
Version
Final published version
Abstract
Increased glucose uptake and metabolism is a prominent phenotype of most cancers, but efforts to clinically target this metabolic alteration have been challenging. Here, we present evidence that lactoylglutathione (LGSH), a byproduct of methylglyoxal detoxification, is elevated in both human and murine non-small cell lung cancers (NSCLC). Methylglyoxal is a reactive metabolite byproduct of glycolysis that reacts non-enzymatically with nucleophiles in cells, including basic amino acids, and reduces cellular fitness. Detoxification of methylglyoxal requires reduced glutathione (GSH), which accumulates to high levels in NSCLC relative to normal lung. Ablation of the methylglyoxal detoxification enzyme glyoxalase I (Glo1) potentiates methylglyoxal sensitivity and reduces tumor growth in mice, arguing that targeting pathways involved in detoxification of reactive metabolites is an approach to exploit the consequences of increased glucose metabolism in cancer.
Subjects
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy
General Chemistry
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s41467-019-13419-4
