ArticleNucleic acids research2019
Exogenous pyruvate represses histone gene expression and inhibits cancer cell proliferation via the NAMPT-NAD+-SIRT1 pathway.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Interplay Between Glucose Metabolism and Chromatin Modifications in Cancer.Frontiers in cell and developmental biology · 2021Pooled it
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- FGF2 Enhances MSCs Secretome Therapy for Skin Photoaging by Delaying Senescence via iNAMPT/AMPK Signaling and Facilitating eNAMPT-Mediated Regenerative Crosstalk.Stem cell reviews and reports · 2026Article
- Gut microbiota-derived butyrate and the SIRT1/FoxO1 axis: epigenetic-metabolic regulation of ovarian function in premature ovarian insufficiency-a comprehensive review.Frontiers in microbiology · 2026Review
- CLK1 is a potential tumor suppressor for NSCLC by regulating cell proliferation and immune infiltration.Frontiers in cell and developmental biology · 2026Article
- MEF2C: A Novel Transcription Factor Implicated in Human Malignant Tumors.Current topics in medicinal chemistry · 2026Review
- Palmitic Acid Induces Dynamic Time-Dependent Alterations in HDACs, Neuronal Chromatin Acetylation, and Gene Expression.Neurochemical research · 2025Article
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- Nicotinamide Mononucleotide: Research Process in Cardiovascular Diseases.International journal of molecular sciences · 2024Review
- Role of the NF-kB signalling pathway in heterotopic ossification: biological and therapeutic significance.Cell communication and signaling : CCS · 2024Review
- Therapeutic potential of Xihuang Pill in colorectal cancer: Metabolomic and microbiome-driven approaches.Frontiers in pharmacology · 2024Article
- The Lipid Metabolism as Target and Modulator of BOLD-100 Anticancer Activity: Crosstalk with Histone Acetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Impact of Opioids on Cellular Metabolism: Implications for Metabolic Pathways Involved in Cancer.Pharmaceutics · 2023Review
- CDK7-YAP-LDHD axis promotes D-lactate elimination and ferroptosis defense to support cancer stem cell-like properties.Signal transduction and targeted therapy · 2023Article
- The metabolic control of DNA replication: mechanism and function.Open biology · 2023Review
- Glc7/PP1 dephosphorylates histone H3T11 to regulate autophagy and telomere silencing in response to nutrient availability.Cell discovery · 2023Article
- Aclarubicin stimulates RNA polymerase II elongation at closely spaced divergent promoters.Science advances · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Pyruvate is a glycolytic metabolite used for energy production and macromolecule biosynthesis. However, little is known about its functions in tumorigenesis. Here, we report that exogenous pyruvate inhibits the proliferation of different types of cancer cells. This inhibitory effect of pyruvate on cell growth is primarily attributed to its function as a signal molecule to repress histone gene expression, which leads to less compact chromatin and misregulation of genome-wide gene expression. Pyruvate represses histone gene expression by inducing the expression of NAD+ biosynthesis enzyme, nicotinamide phosphoribosyltransferase (NAMPT) via myocyte enhancer factor 2C (MEF2C), which then increases NAD+ levels and activates the histone deacetylase activity of SIRT1. Chromatin immunoprecipitation analysis indicates that pyruvate enhances SIRT1 binding at histone gene promoters where it reduces histone acetylation. Although pyruvate delays cell entry into S phase, pyruvate represses histone gene expression independent of cell cycle progression. Moreover, we find that administration of pyruvate reduces histone expression and retards tumor growth in xenograft mice without significant side effects. Using tissues from cervical and lung cancer patients, we find intracellular pyruvate concentrations inversely correlate with histone protein levels. Together, we uncover a previously unknown function of pyruvate in regulating histone gene expression and cancer cell proliferation.
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