ArticleMolecular cancer2013
Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2.
Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 116 citations in OpenAlex.
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
- Pyruvate kinase M2 modulates Japanese encephalitis virus replication in neuronal cells.The Journal of general virology · 2025Article
- PKM2 regulates metabolic flux and oxidative stress in the murine heart.Physiological reports · 2024Article
- The Role of PKM2 in Multiple Signaling Pathways Related to Neurological Diseases.Molecular neurobiology · 2024Review
- Changes in Cells Associated with Insulin Resistance.International journal of molecular sciences · 2024Review
- Insulin Resistance: The Increased Risk of Cancers.Current oncology (Toronto, Ont.) · 2024Review
- In Vitro Simulated Ketogenic Diet Inhibits the Proliferation and Migration of Liver Cancer Cells by Reducing Insulin Production and Down-regulating FOXC2 Expression.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024Article
- Astaxanthin and DHA supplementation ameliorates the proteomic profile of perinatal undernutrition-induced adipose tissue dysfunction in adult life.Scientific reports · 2023Article
- The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases.PNAS nexus · 2023Article
- Unlocking the role of lactate: metabolic pathways, signaling, and gene regulation in postmitotic retinal cells.Frontiers in ophthalmology · 2023Review
- HPV18 oncoproteins driven expression of PKM2 reprograms HeLa cell metabolism to maintain aerobic glycolysis and viability.Virusdisease · 2022Article
- Oncogenic TRIB2 interacts with and regulates PKM2 to promote aerobic glycolysis and lung cancer cell procession.Cell death discovery · 2022Article
- Reprogramming Carbohydrate Metabolism in Cancer and Its Role in Regulating the Tumor Microenvironment.Sub-cellular biochemistry · 2022Article
- The Intricate Crosstalk Between Insulin and Pancreatic Ductal Adenocarcinoma: A Review From Clinical to Molecular.Frontiers in cell and developmental biology · 2022Review
- Tumor pyruvate kinase M2 modulators: a comprehensive account of activators and inhibitors as anticancer agents.RSC medicinal chemistry · 2021Review
- Metabolic pathways in obesity-related breast cancer.Nature reviews. Endocrinology · 2021Review
- The pyruvate kinase activator mitapivat reduces hemolysis and improves anemia in a β-thalassemia mouse model.The Journal of clinical investigation · 2021Article
- HMGCR inhibition stabilizes the glycolytic enzyme PKM2 to support the growth of renal cell carcinoma.PLoS biology · 2021Article
- A Warburg-like metabolic program coordinates Wnt, AMPK, and mTOR signaling pathways in epileptogenesis.PloS one · 2021Article
- PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation.The Journal of experimental medicine · 2020Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInsulin is tightly associated with cancer progression; however, mechanistic insights into such observations are poorly understood. Recent studies show that metabolic transformation is critical to cancer cell proliferation. Here, we attempt to understand the role of insulin in promotion of cancer metabolism. To this end, the role of insulin in regulating glycolytic enzyme pyruvate kinase M2 (PKM2) was examined.
resultsWe observed that insulin up-regulated PKM2 expression, through PI3K/mTOR mediated HIF1α induction, but significantly reduced PKM2 activity independent of this pathway. Drop in PKM2 activity was attributed to subunit dissociation leading to formation of low activity PKM2 oligomers, as assessed by density gradient centrifugation. However, tyrosine 105 phosphorylation of PKM2, known for inhibiting PKM2 activity, remained unaffected on insulin treatment. Interestingly, insulin-induced ROS was found responsible for PKM2 activity reduction. The observed changes in PKM2 status led to augmented cancer metabolism. Insulin-induced PKM2 up-regulation resulted in enhanced aerobic glycolysis as confirmed by PKM2 knockdown studies. Further, PKM2 activity reduction led to characteristic pooling of glycolytic intermediates and increased accumulation of NADPH; suggesting diversion of glucose flux towards macromolecular synthesis, necessary for cancer cell growth.
conclusionThe study identifies new PKM2-mediated effects of insulin on cancer metabolism, thus, advancing the understanding of insulin's role in cancer.
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