ArticleThe Journal of biological chemistry2020
Evolved resistance to partial GAPDH inhibition results in loss of the Warburg effect and in a different state of glycolysis.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Repurposing Disulfiram for Cancer Therapy: Mechanistic Insights and Translational Challenges.International journal of molecular sciences · 2026Review
- Targeting Glycolytic Metabolism in Cancer Therapy: Current Approaches and Future Perspectives.Cells · 2026Review
- Is heptelidic (koningic) acid a microbial hormone that regulates secondary metabolism in the biocontrol fungus Trichoderma virens?Current genetics · 2025Article
- MYO1F regulates T-cell activation and glycolytic metabolism by promoting the acetylation of GAPDH.Cellular & molecular immunology · 2025Article
- ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis.Gland surgery · 2024Article
- Copper in the colorectal cancer microenvironment: pioneering a new era of cuproptosis-based therapy.Frontiers in oncology · 2024Review
- The Illustration of Altered Glucose Dependency in Drug-Resistant Cancer Cells.International journal of molecular sciences · 2023Review
- Acute Hypoxia Alters Extracellular Vesicle Signatures and the Brain Citrullinome of Naked Mole-Rats (International journal of molecular sciences · 2022Article
- Ginkgolide A Participates in LPS-Induced PMVEC Injury by Regulating miR-224 and Inhibiting p21 in a Targeted Manner.Contrast media & molecular imaging · 2022Article
- A "Weird" Mitochondrial Fatty Acid Oxidation as a Metabolic "Secret" of Cancer.Oxidative medicine and cellular longevity · 2022Review
- Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer.Molecular medicine reports · 2021Article
- Disruption of the Complex between GAPDH and Hsp70 Sensitizes C6 Glioblastoma Cells to Hypoxic Stress.International journal of molecular sciences · 2021Article
- Targeting of Evolutionarily Acquired Cancer Cell Phenotype by Exploiting pHi-Metabolic Vulnerabilities.Cancers · 2020Article
- Glyceraldehyde-3-phosphate Dehydrogenase is a Multifaceted Therapeutic Target.Pharmaceutics · 2020Review
- Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate.Frontiers in pharmacology · 2019Review
- Determining the quantitative relationship between glycolysis and GAPDH in cancer cells exhibiting the Warburg effect.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Aerobic glycolysis or the Warburg effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although the WE is ubiquitous, its biological role remains controversial, and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, here we evolved resistance to koningic acid (KA), a natural product that specifically inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme, during the WE. We found that KA-resistant cells lose the WE but continue to conduct glycolysis and surprisingly remain dependent on glucose as a carbon source and also on central carbon metabolism. Consequently, this altered state of glycolysis led to differential metabolic activity and requirements, including emergent activities in and dependences on fatty acid metabolism. These findings reveal that aerobic glycolysis is a process functionally distinct from conventional glucose metabolism and leads to distinct metabolic requirements and biological functions.
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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.