ArticleCell research2018
Pyruvate kinase M2 regulates homologous recombination-mediated DNA double-strand break repair.
Article in Cell research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
55 citing papers in PubMed, 74 citations in OpenAlex.
- PKM2-Mediated Glycolytic Reprogramming in Thyroid Cancer: Mechanistic Insights and Therapeutic Potential.Molecules (Basel, Switzerland) · 2026Review
- ATM promotes PFKP nuclear translocation to balance glycolysis and homologous recombination repair.Nucleic acids research · 2026Article
- Precise metabolomics identifies glycolysis-related pyruvate kinase M activity as regulator of the S-phase-specific radiation response in triple-negative breast cancer cells.Cell communication and signaling : CCS · 2026Article
- Hallmarks of nuclear metabolism: implications for genome integrity, nuclear signaling, and therapeutic targeting.npj metabolic health and disease · 2026Review
- Regulation of drug resistance in bladder urothelial carcinoma by tumor aerobic glycolysis.Journal of translational medicine · 2025Review
- Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer treatment?Acta pharmacologica Sinica · 2025Review
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- Article
- Moonlighting functions of glucose metabolic enzymes and metabolites in cancer.Nature reviews. Cancer · 2025Review
- Impact of glycolysis enzymes and metabolites in regulating DNA damage repair in tumorigenesis and therapy.Cell communication and signaling : CCS · 2025Review
- Nucleus-translocated GCLM promotes chemoresistance in colorectal cancer through a moonlighting function.Nature communications · 2025Article
- The role and therapeutic potential of glucose metabolism in multidrug resistance of cancer.Frontiers in cell and developmental biology · 2025Review
- The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities.Neoplasia (New York, N.Y.) · 2024Review
- Nuclear translocation of nucleotide enzyme Phosphoglucomutase 2 governs DNA damage response and anti-tumor immunity.Heliyon · 2024Article
- Interplay between altered metabolism and DNA damage and repair in ovarian cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- YZL-51N functions as a selective inhibitor of SIRT7 by NADiScience · 2024Article
- The role of PKM2 in cancer progression and its structural and biological basis.Journal of physiology and biochemistry · 2024Review
- CircCDYL2 bolsters radiotherapy resistance in nasopharyngeal carcinoma by promoting RAD51 translation initiation for enhanced homologous recombination repair.Journal of experimental & clinical cancer research : CR · 2024Article
- GINv2.0: a comprehensive topological network integrating molecular interactions from multiple knowledge bases.NPJ systems biology and applications · 2024Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Resistance to genotoxic therapies is a primary cause of treatment failure and tumor recurrence. The underlying mechanisms that activate the DNA damage response (DDR) and allow cancer cells to escape the lethal effects of genotoxic therapies remain unclear. Here, we uncover an unexpected mechanism through which pyruvate kinase M2 (PKM2), the highly expressed PK isoform in cancer cells and a master regulator of cancer metabolic reprogramming, integrates with the DDR to directly promote DNA double-strand break (DSB) repair. In response to ionizing radiation and oxidative stress, ATM phosphorylates PKM2 at T328 resulting in its nuclear accumulation. pT328-PKM2 is required and sufficient to promote homologous recombination (HR)-mediated DNA DSB repair through phosphorylation of CtBP-interacting protein (CtIP) on T126 to increase CtIP's recruitment at DSBs and resection of DNA ends. Disruption of the ATM-PKM2-CtIP axis sensitizes cancer cells to a variety of DNA-damaging agents and PARP1 inhibition. Furthermore, increased nuclear pT328-PKM2 level is associated with significantly worse survival in glioblastoma patients. Combined, these data advocate the use of PKM2-targeting strategies as a means to not only disrupt cancer metabolism but also inhibit an important mechanism of resistance to genotoxic therapies.
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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.