Increased antioxidative defense and reduced advanced glycation end-product formation by metabolic adaptation in Non-Small-Cell-Lung-Cancer patients

ABSTRACT: Oxidative stress is a critical driver of lung cancer progression, causing DNA and protein instability and supporting oncogenic transformation. On metabolic level, mediators of oxidative stress, reactive oxygen species (ROS), can oxidatively modify metabolic enzymes and reroute metabolic pathways according to tumor needs. The main carriers of redox signals are thiol groups, which due to their reactive nature are rarely analyzed in a clinical setting. To accurately address the cross talk between redox signaling and metabolism in lung cancer, we carefully collected tumor as well as neighboring healthy tissue from 70 individuals with non-small cell lung cancer: samples were collected at the point of surgical tumor removal and preserved immediately in a thiol-quenching organic solvent solution, before being subjected to redox-proteomics analysis. As a result of such an unbiased and meticulous approach we for the first time report ex vivo evidence of higher oxidation of a number of key metabolic enzymes in tumor tissue, especially those involved in glucose metabolism. We furthermore demonstrate evidence of the tumor striving to maintain functional oxidative metabolism amid the prominent rise of intracellular oxidative stress. Lastly, we report both redox and protein level deactivation of the glyoxalase system, which might be compensated by higher excretion of toxic methylglyoxal into the blood stream and/or higher GAPDH activity preserving cancer progression.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung

DISEASE(S): Lung Adenocarcinoma,Lung Squamous Cell Carcinoma

SUBMITTER: Laura Liesinger  

LAB HEAD: Ruth Birner-Gruenberger

PROVIDER: PXD052340 | Pride | 2025-05-12

REPOSITORIES: Pride