ArticleNature communications2014
Reduced methylation of PFKFB3 in cancer cells shunts glucose towards the pentose phosphate pathway.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 247 citations in OpenAlex.
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- Epigenetics-mediated pathological alterations and their diagnostic and therapeutic potential in sepsis-associated acute kidney injury.Clinical epigenetics · 2026Review
- Protein arginine methyltransferases in cancer: mechanisms, functions, and therapeutic opportunities.Journal of biomedical science · 2026Review
- Targeting aerobic glycolysis combats tyrosine kinase inhibitor resistance of hepatocellular carcinoma.International journal of cancer · 2026Review
- Role of cystathionine-β-synthase and hydrogen sulfide in down syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- The lactylation of glucose-6-phosphate dehydrogenase promotes malignant phenotypes in cancer cell lines.Molecular biology reports · 2025Article
- Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis.Nature communications · 2025Article
- ERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth.Nature structural & molecular biology · 2025Article
- Metabolic regulation by p53: Implications for cancer therapy.Molecules and cells · 2025Review
- Metabolic reprogramming and interventions in angiogenesis.Journal of advanced research · 2025Review
- Control of circadian muscle glucose metabolism through the BMAL1-HIF axis in obesity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The role and therapeutic potential of glucose metabolism in multidrug resistance of cancer.Frontiers in cell and developmental biology · 2025Review
- PFKFB3-dependent redox homeostasis and DNA repair support cell survival under EGFR-TKIs in non-small cell lung carcinoma.Cancer & metabolism · 2024Article
- Identification of PFKFB3 as a key factor in the development of colorectal cancer and immunotherapy resistance.Clinical and experimental medicine · 2024Article
- Role of PRMT1 and PRMT5 in Breast Cancer.International journal of molecular sciences · 2024Review
- PRMT1 promotes Warburg effect by regulating the PKM2/PKM1 ratio in non-small cell lung cancer.Cell death & disease · 2024Article
- Article
- PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer.Cancer research · 2024Article
- Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis.Journal of translational medicine · 2024Article
- CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR-212-5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Haem oxygenase (HO)-1/carbon monoxide (CO) protects cancer cells from oxidative stress, but the gas-responsive signalling mechanisms remain unknown. Here we show using metabolomics that CO-sensitive methylation of PFKFB3, an enzyme producing fructose 2,6-bisphosphate (F-2,6-BP), serves as a switch to activate phosphofructokinase-1, a rate-limiting glycolytic enzyme. In human leukaemia U937 cells, PFKFB3 is asymmetrically di-methylated at R131 and R134 through modification by protein arginine methyltransferase 1. HO-1 induction or CO results in reduced methylation of PFKFB3 in varied cancer cells to suppress F-2,6-BP, shifting glucose utilization from glycolysis toward the pentose phosphate pathway. Loss of PFKFB3 methylation depends on the inhibitory effects of CO on haem-containing cystathionine β-synthase (CBS). CBS modulates remethylation metabolism, and increases NADPH to supply reduced glutathione, protecting cells from oxidative stress and anti-cancer reagents. Once the methylation of PFKFB3 is reduced, the protein undergoes polyubiquitination and is degraded in the proteasome. These results suggest that the CO/CBS-dependent regulation of PFKFB3 methylation determines directional glucose utilization to ensure resistance against oxidative stress for cancer cell survival.
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