ArticleMolecular cell2022
Methionine oxidation activates pyruvate kinase M2 to promote pancreatic cancer metastasis.
Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- Metabolites and cancer metastasis.Oncogene · 2026Review
- An iron-regulated methionine redox axis governs adipose browning and cancer cachexia.Nature cancer · 2026Article
- Choline metabolism drives metastasis in BRCA1-deficient ovarian cancers by activating FAM3C.Nature communications · 2026Article
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Chiral methionine oxidation reagents reveal stereospecific proteome modifications.bioRxiv : the preprint server for biology · 2026Article
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Proteomic Profiling of Oxidative Stress Response Proteins with a Methionine Sulfoxide-Inspired Activity-Based Probe.JACS Au · 2026Article
- Integrative Omics Defines Metabolic Biomarkers and Genetic Regulatory Mechanisms of Mortality Risk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence.The EMBO journal · 2025Review
- Molecular Imaging: Unveiling Metabolic Abnormalities in Pancreatic Cancer.International journal of molecular sciences · 2025Review
- Ketogenic diet prevents obesity-associated pancreatic cancer independent of weight loss and induces pancreatic metabolic reprogramming.bioRxiv : the preprint server for biology · 2025Article
- Redox Balance in Cancer in the Context of Tumor Prevention and Treatment.Biomedicines · 2025Review
- Risk of serum circulating environmental chemical residues to esophageal squamous cell carcinoma: a nested case-control metabolome-wide association study.Analytical and bioanalytical chemistry · 2025Article
- PKM2, the "K+ sink" in the tumor interstitial fluid.Protein & cell · 2025Article
- Nudix Hydrolase 13 Impairs the Initiation of Colorectal Cancer by Inhibiting PKM1 ADP-Ribosylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Identification and validation of cholesterol metabolism-related gene GNB3 as prognosis biomarker for pancreatic adenocarcinoma.Discover oncology · 2025Article
- Emerging opportunities for intact and native protein analysis using chemical proteomics.Analytica chimica acta · 2025Review
- Demystifying metabolic‒immune crosstalk: how amino acid metabolic reprogramming shapes the malignant phenotype and macrophage polarization of biliary and pancreatic tumors.International journal of biological sciences · 2025Review
- A comprehensive multi-omics analysis uncovers the associations between gut microbiota and pancreatic cancer.Frontiers in microbiology · 2025Article
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Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
Abstract
Cancer mortality is primarily a consequence of its metastatic spread. Here, we report that methionine sulfoxide reductase A (MSRA), which can reduce oxidized methionine residues, acts as a suppressor of pancreatic ductal adenocarcinoma (PDA) metastasis. MSRA expression is decreased in the metastatic tumors of PDA patients, whereas MSRA loss in primary PDA cells promotes migration and invasion. Chemoproteomic profiling of pancreatic organoids revealed that MSRA loss results in the selective oxidation of a methionine residue (M239) in pyruvate kinase M2 (PKM2). Moreover, M239 oxidation sustains PKM2 in an active tetrameric state to promote respiration, migration, and metastasis, whereas pharmacological activation of PKM2 increases cell migration and metastasis in vivo. These results demonstrate that methionine residues can act as reversible redox switches governing distinct signaling outcomes and that the MSRA-PKM2 axis serves as a regulatory nexus between redox biology and cancer metabolism to control tumor metastasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.