Reactive metabolite production is a targetable liability of glycolytic metabolism in lung cancer View Full Text


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Article Info

DATE

2019-12-06

AUTHORS

Alba Luengo, Keene L. Abbott, Shawn M. Davidson, Aaron M. Hosios, Brandon Faubert, Sze Ham Chan, Elizaveta Freinkman, Lauren G. Zacharias, Thomas P. Mathews, Clary B. Clish, Ralph J. DeBerardinis, Caroline A. Lewis, Matthew G. Vander Heiden

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. More... »

PAGES

5604

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-13419-4

    DOI

    http://dx.doi.org/10.1038/s41467-019-13419-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1123151436

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31811141


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