Active Oxidative Metabolism and Impaired Glyoxalase System Under Increased Intracellular Oxidative Stress in Non-Small Cell Lung Cancer

Abstract

Reactive oxygen species can oxidatively modify enzymes to reroute metabolic pathways according to tumor needs but we lack overview of all potential targets. Thiol groups are most susceptible to oxidative modifications but rarely analyzed in clinical settings due to their reactivity. To accurately address the cross-talk between redox signaling and metabolism we collected tumor and healthy tissue from 70 individuals with non-small cell lung cancer right after surgery into a thiol-quenching solution, then carried out redox-proteomics. As a result of such an unbiased approach, we for the first time show evidence of higher oxidation of a number of key metabolic enzymes in tumor (especially glucose-related); we demonstrate that cancer strives to maintain oxidative metabolism amid the rise of intracellular oxidative stress; and report both redox and protein level deactivation of the glyoxalase system, which might be compensated by higher excretion or lower production of toxic methylglyoxal, aiding cancer progression.