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Updated: Sep 15, 2026
Extraction of Aqueous Metabolites from Cultured Adherent Cells for Metabolomic Analysis by Capillary Electrophoresis-Mass Spectrometry
Published on: June 9, 2019
Integrating proteomics and metabolomics to reveal MAT2A for metabolic reprogramming in non-small cell lung cancer
Yimin Chen1,2, Yuxi Liu1,3, Zhenyun Zhu1
1Analytical Research Center for Organic and Biological Molecules, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Abstract:
Methionine adenosyltransferase 2A (MAT2A) links metabolic reprogramming to epigenetic regulation via S-adenosylmethionine (SAM) production, but its role in non-small cell lung cancer (NSCLC) remains unclear, and current inhibitors require combination strategies. Using proteomics and metabolomics in NSCLC cells treated with MAT2A-targeting siRNA or the inhibitor AG-270, we characterized MAT2A-driven metabolic rewiring. In fatty acid biosynthesis, MAT2A regulates FASN and SCD; exogenous palmitic acid reverses AG-270-induced growth inhibition, supporting combination with the FASN inhibitor TVB-2640. In cholesterol metabolism, MAT2A modulates biosynthesis and efflux, and an LXR agonist promoting cholesterol efflux enhances AG-270 efficacy. In energy metabolism, MAT2A governs glycolysis via HIF1A, and a GLUT1 inhibitor synergizes with AG-270. In the transsulfuration pathway, MAT2A transcriptionally regulates CBS and shows synergy with inhibitors of PHGDH (producing serine for cysteine biosynthesis) and SLC7A11 (mediating cysteine uptake). Collectively, our findings establish MAT2A as a central metabolic regulator in NSCLC and propose rational combination strategies.
