ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Pyruvate Facilitates FACT-Mediated γH2AX Loading to Chromatin and Promotes the Radiation Resistance of Glioblastoma.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.Experimental hematology & oncology · 2026Review
- USP7 facilitates brain tumor survival upon glucose deprivation by regulating phosphofructokinase muscle-type nuclear translocation in mice.PLoS biology · 2026Article
- ACSS1 co-opts acetyl-CoA metabolism to drive DNA repair and undermine radiotherapy efficacy in breast cancer.Cell death & disease · 2025Article
- Review
- PTEN/PKM2/ERα-Driven Glyoxalase 1 Overexpression Sustains PC3 Prostate Cancer Cell Growth Through MG-H1/RAGE Pathway Desensitization Leading to HAntioxidants (Basel, Switzerland) · 2025Article
- Histone Phosphorylation in DNA Damage Response.International journal of molecular sciences · 2025Review
- Copy number amplification of FLAD1 promotes the progression of triple-negative breast cancer through lipid metabolism.Nature communications · 2025Article
- Impact of glycolysis enzymes and metabolites in regulating DNA damage repair in tumorigenesis and therapy.Cell communication and signaling : CCS · 2025Review
- The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities.Neoplasia (New York, N.Y.) · 2024Review
- Review
- Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells.Experimental hematology & oncology · 2024Review
- Hypoxic microenvironment-induced exosomes confer temozolomide resistance in glioma through transfer of pyruvate kinase M2.Discover oncology · 2024Article
- The Noncanonical Functions of Metabolites in Tumor Progression.Metabolites · 2024Review
- TAB182 regulates glycolytic metabolism by controlling LDHA transcription to impact tumor radiosensitivity.Cell death & disease · 2024Article
- The regulation of cell homeostasis and antiviral innate immunity by autophagy during classical swine fever virus infection.Emerging microbes & infections · 2023Article
- M2 isoform of pyruvate kinase rewires glucose metabolism during radiation therapy to promote an antioxidant response and glioblastoma radioresistance.Neuro-oncology · 2023Article
- Bioengineered Bacteriophage-Like Nanoparticles as RNAi Therapeutics to Enhance Radiotherapy against Glioblastomas.ACS nano · 2023Article
- Melatonin inhibits bladder tumorigenesis by suppressing PPARγ/ENO1-mediated glycolysis.Cell death & disease · 2023Article
- A Mouse Systems Genetics Approach Reveals Common and Uncommon Genetic Modifiers of Hepatic Lysosomal Enzyme Activities and Glycosphingolipids.International journal of molecular sciences · 2023Article
- RBX1 regulates PKM alternative splicing to facilitate anaplastic thyroid carcinoma metastasis and aerobic glycolysis by destroying the SMAR1/HDAC6 complex.Cell & bioscience · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
DNA repair confers the resistance of tumor cells to DNA-damaging anticancer therapies, while how reprogrammed metabolism in tumor cells contributes to such process remains poorly understood. Pyruvate kinase M2 isoform (PKM2) catalyzes the conversion of phosphoenolpyruvate to pyruvate and regulates the last rate-limiting step of glycolysis. Here it is shown that the glycolytic metabolite pyruvate enhances DNA damage repair by facilitating chromatin loading of γH2AX, thereby promoting the radiation resistance of glioma cells. Mechanistically, PKM2 is phosphorylated at serine (S) 222 upon DNA damage and interacts with FACT complex, a histone chaperone comprising SPT16 and SSRP1 subunit. The pyruvate produced by PKM2 directly binds to SSRP1, which increases the association of FACT complex with γH2AX and subsequently facilitates FACT-mediated chromatin loading of γH2AX, ultimately promoting DNA repair and tumor cell survival. Intriguingly, the supplementation of exogenous pyruvate can also sufficiently enhance FACT-mediated chromatin loading of γH2AX and promotes tumor cell survival upon DNA damage. The levels of PKM2 S222 phosphorylation correlate with the malignancy and prognosis of human glioblastoma. The finding demonstrates a novel mechanism by which PKM2-produced pyruvate promotes DNA repair by regulating γH2AX loading to chromatin and establishes a critical role of this mechanism in glioblastoma radiation resistance.
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Registered trials
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