ArticleChinese journal of cancer research = Chung-kuo yen cheng yen chiu2019
Hexokinase II promotes the Warburg effect by phosphorylating alpha subunit of pyruvate dehydrogenase.
Article in Chinese journal of cancer research = Chung-kuo yen cheng yen chiu, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 33 citations in OpenAlex.
- Exercise-induced protein lactylation: From molecular mechanisms to precision health applications.iScience · 2026Review
- Metabolism-related ALDH1B1 acts as potential predictor and therapeutic target for primary gastrointestinal diffuse large B-cell lymphoma.Apoptosis : an international journal on programmed cell death · 2025Article
- Metabolic reprogramming in cancer and senescence.MedComm · 2025Review
- Emerging roles of metabolic biomarkers in renal cell carcinoma: from molecular mechanisms to clinical implications.Frontiers in cell and developmental biology · 2025Review
- Chronic stress enhances glycolysis and promotes tumorigenesis.Frontiers in oncology · 2025Article
- Strategies to Overcome Intrinsic and Acquired Resistance to Chemoradiotherapy in Head and Neck Cancer.Cells · 2024Review
- Mitochondrion: Main organelle in orchestrating cancer escape from chemotherapy.Cancer reports (Hoboken, N.J.) · 2024Review
- Formyl-peptide receptor 2 signalling triggers aerobic metabolism of glucose through Nox2-dependent modulation of pyruvate dehydrogenase activity.Open biology · 2023Article
- Experimental evidence and clinical implications of Warburg effect in the skeletal muscle of Fabry disease.iScience · 2023Article
- Real-time resolution studies of the regulation of pyruvate-dependent lactate metabolism by hexokinases in single cells.PloS one · 2023Article
- Cuproptosis-Related Genes Are Associated with Cell Cycle and Serve as the Prognostic Signature for Clear Cell Renal Cell Carcinoma.Journal of clinical medicine · 2022Article
- Long non-coding RNA SLC2A1-AS1 induced by GLI3 promotes aerobic glycolysis and progression in esophageal squamous cell carcinoma by sponging miR-378a-3p to enhance Glut1 expression.Journal of experimental & clinical cancer research : CR · 2021Article
- CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt.Journal of cellular and molecular medicine · 2021Article
- Pyruvate Dehydrogenase Contributes to Drug Resistance of Lung Cancer Cells Through Epithelial Mesenchymal Transition.Frontiers in cell and developmental biology · 2021Article
- A Comprehensive Proteome and Acetyl-Proteome Atlas Reveals Molecular Mechanisms Adapting to the Physiological Changes From Pre-laying to Peak-Laying Stage in Liver of Hens (Frontiers in veterinary science · 2021Article
- Vitamin C activates pyruvate dehydrogenase (PDH) targeting the mitochondrial tricarboxylic acid (TCA) cycle in hypoxicTheranostics · 2021Article
- New drugs are not enough‑drug repositioning in oncology: An update.International journal of oncology · 2020Review
- SREBP-1 inhibitor Betulin enhances the antitumor effect of Sorafenib on hepatocellular carcinoma via restricting cellular glycolytic activity.Cell death & disease · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTumor cells rely heavily on glycolysis regardless of oxygen tension, a phenomenon called the Warburg effect. Hexokinase II (HKII) catalyzes the first irreversible step of glycolysis and is often overexpressed in tumor cells. Mitochondrial HKII couples glycolysis and oxidative phosphorylation while maintaining mitochondrial membrane integrity. In this study, we investigated the role of HKII in promoting the Warburg effect in cancer cells.
methodsHKII-mediated phosphorylation of the alpha subunit of pyruvate dehydrogenase (PDHA1) was tested in HEK293T cells and clear cell renal cell carcinoma (ccRCC) specimens using gene knockdown, western blotting, immunohistochemistry, and immunofluorescence.
resultsIt was determined that HKII could not only transform glucose into glucose-6-phosphate, but also transfer the phosphate group of ATP onto PDHA1. In addition, it was found that HKII increased the phosphorylation of Ser293 on PDHA1, decreasing pyruvate dehydrogenase (PDH) complex activity and thus rerouting the metabolic pathway and promoting the Warburg effect. The overexpression of HKII correlated with the phosphorylation of PDHA1 and disease progression in ccRCC.
conclusionsThe data presented here suggest that HKII is an important biomarker in the evaluation and treatment of cancer.
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