ArticleThe Journal of biological chemistry2016
Activation of AMP-activated Protein Kinase by Metformin Induces Protein Acetylation in Prostate and Ovarian Cancer Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Observational Studies on the Association Between Post-diagnostic Metformin Use and Survival in Ovarian Cancer: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2019Pooled it
- Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer.JCI insight · 2020Trial
- Comparison of Metformin Combinations with Other Repurposed Drugs in the Treatment of Hamster Fibrosarcoma: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Metformin-A Type 2 Diabetes Mellitus Drug-And Ovarian Cancer: Anticancer Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- Metformin Impairs Breast Cancer Growth through the Inhibition of PRMT6.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metformin as a Metabolic Adjuvant to Amoxicillin: A Hypothesis on Synergistic Antibacterial Action.Advanced pharmaceutical bulletin · 2025Article
- Exploring Cirrhosis: Insights into Advances in Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Lipids: Driving Forces in the Underlying Biology of Carcinogenesis.ACS pharmacology & translational science · 2025Review
- Guanidinoacetic acid regulated postmortem muscle glycolysis associated with AMPK signaling and protein acetylation.Animal bioscience · 2025Article
- Metformin Effects on SHIP2, AMPKs and Gut Microbiota: Recent Updates on Pharmacology.Current medicinal chemistry · 2025Review
- Roles of posttranslational modifications in lipid metabolism and cancer progression.Biomarker research · 2024Review
- Augmented Global Protein Acetylation Diminishes Cell Growth and Migration of Cholangiocarcinoma Cells.International journal of molecular sciences · 2024Article
- Activation of AMPK inhibits cervical cancer growth by hyperacetylation of H3K9 through PCAF.Cell communication and signaling : CCS · 2024Article
- Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.Biology · 2024Review
- Metformin and its potential influence on cell fate decision between apoptosis and senescence in cancer, with a special emphasis on glioblastoma.Frontiers in oncology · 2024Review
- Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins.International journal of molecular sciences · 2023Review
- The enhancement of CRISPR/Cas9 gene editing using metformin.Biochemistry and biophysics reports · 2023Article
- Tumor metabolism rewiring in epithelial ovarian cancer.Journal of ovarian research · 2023Review
- Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis.Science advances · 2023Article
- Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
AMP-activated protein kinase (AMPK) is an energy sensor and master regulator of metabolism. AMPK functions as a fuel gauge monitoring systemic and cellular energy status. Activation of AMPK occurs when the intracellular AMP/ATP ratio increases and leads to a metabolic switch from anabolism to catabolism. AMPK phosphorylates and inhibits acetyl-CoA carboxylase (ACC), which catalyzes carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting reaction in de novo synthesis of fatty acids. AMPK thus regulates homeostasis of acetyl-CoA, a key metabolite at the crossroads of metabolism, signaling, chromatin structure, and transcription. Nucleocytosolic concentration of acetyl-CoA affects histone acetylation and links metabolism and chromatin structure. Here we show that activation of AMPK with the widely used antidiabetic drug metformin or with the AMP mimetic 5-aminoimidazole-4-carboxamide ribonucleotide increases the inhibitory phosphorylation of ACC and decreases the conversion of acetyl-CoA to malonyl-CoA, leading to increased protein acetylation and altered gene expression in prostate and ovarian cancer cells. Direct inhibition of ACC with allosteric inhibitor 5-(tetradecyloxy)-2-furoic acid also increases acetylation of histones and non-histone proteins. Because AMPK activation requires liver kinase B1, metformin does not induce protein acetylation in liver kinase B1-deficient cells. Together, our data indicate that AMPK regulates the availability of nucleocytosolic acetyl-CoA for protein acetylation and that AMPK activators, such as metformin, have the capacity to increase protein acetylation and alter patterns of gene expression, further expanding the plethora of metformin's physiological effects.
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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.