The Warburg Effect: How Does it Benefit Cancer Cells?
Open accessAbstract
Cancer cells rewire their metabolism to promote growth, survival, proliferation, and long-term maintenance. The common feature of this altered metabolism is the increased glucose uptake and fermentation of glucose to lactate. This phenomenon is observed even in the presence of completely functioning mitochondria and, together, is known as the 'Warburg Effect'. The Warburg Effect has been documented for over 90 years and extensively studied over the past 10 years, with thousands of papers reporting to have established either its causes or its functions. Despite this intense interest, the function of the Warburg Effect remains unclear. Here, we analyze several proposed explanations for the function of Warburg Effect, emphasize their rationale, and discuss their controversies.
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This metabolic reprogramming supports rapid and sustained proliferation by generating ATP, maintaining redox homeostasis, and diverting glycolytic intermediates into biosynthetic pathways required for macromolecular synthesis.
“This metabolic reprogramming supports rapid and sustained proliferation by generating ATP, maintaining redox homeostasis, and diverting glycolytic intermediates into biosynthetic pathways required for macromolecular synthesis (Vander Heiden et al. 2009;Liberti and Locasale 2016).”
From Primary cell cultures versus immortalized cell lines: critical comparative insights into biological fidelity and translational applications (2026) · cites this paper as Liberti and Locasale 2016
The sections on rapid ATP synthesis, biosynthesis, and cell signaling describe ATP production, diversion of glycolytic intermediates into macromolecule synthesis, and pathways linked to redox homeostasis. But the paper presents these as proposed benefits of the Warburg effect, notes that the ATP and biosynthesis explanations need further study, and does not establish that all three mechanisms sustain proliferation as the citing sentence states. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMetabolic phenotype of immortalized cell lines may diverge from native metabolic profile of their tissue of origin.
“As a result, the metabolic phenotype of immortalized cell lines may diverge from the native metabolic profile of their tissue of origin (Vander Heiden et al. 2009;Liberti and Locasale 2016).”
From Primary cell cultures versus immortalized cell lines: critical comparative insights into biological fidelity and translational applications (2026) · cites this paper as Liberti and Locasale 2016
The Glucose Metabolism and the Warburg Effect section (page unavailable) describes altered glucose metabolism in tumors and other proliferating cells, but does not compare immortalized cell lines with their tissues of origin. Searches for immortalized cell lines, tissue of origin, and differences between cultured cells and tumors found no passage addressing that comparison. (LLM, conf=0.72)
Experimental — accuracy not yet measuredThis metabolic shift, the Warburg effect, is necessary for tumours to survive and multiply.
“This metabolic reprogramming, also known as the Warburg effect, is essential for tumour survival and proliferation45.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [45]
Cancer cells rely on aerobic glycolysis as their primary energy resource (the Warburg effect).
“Unlike normal cells, which derive most of their energy from mitochondrial oxidative phosphorylation, cancer cells rely on aerobic glycolysis as their primary energy resource. This process is recognized as the “Warburg effect”21–23.”
From RETRACTED ARTICLE: Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression (2020) · cites this paper as [23]
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“As a result, the metabolic phenotype of immortalized cell lines may diverge from the native metabolic profile of their tissue of origin (Vander Heiden et al. 2009; Liberti and Locasale 2016).”
- Authors
- Liberti, M. V., & Locasale, J. W.
- Affiliations
- Duke University (US)
- Corresponding author
- Locasale, Jason W.
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 41
- Issue
- 3
- Pages
- 211-218
- ISSN
- 0968-0004 (ISSN-L)
- PMC
- PMC4783224
- OpenAlex
- W2223535266
- Cited by
- 5,150
- References
- 63
- Citations by year
- 2026: 533 · 2025: 672 · 2024: 766 · 2023: 710 · 2022: 623 · 2021: 627 · 2020: 502 · 2019: 348 · 2018: 218 · 2017: 120 · 2016: 26 · 2014: 1 · 2013: 1
- FWCI
- 21.76
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-03-01)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Trends in Biochemical Sciences (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Health (R00CA168997, R01CA193256, T32GM007273)
- National Science Foundation
- Sloan Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- Warburg effect, cancer metabolism, aerobic glycolysis, glucose uptake, lactic acid production, mitochondrial function, tumor cell proliferation, tumor cell survival, metabolic reprogramming
- MeSH terms
- Adenosine Triphosphate, Glucose, Humans, NAD, Neoplasms, Signal Transduction
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