Roles of p53, MYC and HIF-1 in regulating glycolysis–the seventh hallmark of cancer
Open accessAbstract
Despite diversity in genetic events in oncogenesis, cancer cells exhibit a common set of functional characteristics. Otto Warburg discovered that cancer cells have consistently higher rates of glycolysis than normal cells. The underlying mechanisms leading to the Warburg phenomenon include mitochondrial changes, upregulation of rate-limiting enzymes/proteins in glycolysis and intracellular pH regulation, hypoxia-induced switch to anaerobic metabolism, and metabolic reprogramming after loss of p53 function. The regulation of energy metabolism can be traced to a "triad" of transcription factors: c-MYC, HIF-1 and p53. Oncogenetic changes involve a nonrandom set of gene deletions, amplifications and mutations, and many oncogenes and tumor suppressor genes cluster along the signaling pathways that regulate c-MYC, HIF-1 and p53. Glycolysis in cancer cells has clinical implications in cancer diagnosis, treatment and interaction with diabetes mellitus. Many drugs targeting energy metabolism are in development. Future advances in technology may bring about transcriptome and metabolome-guided chemotherapy.
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MYC upregulates glycolysis, DNA-synthesis, and nucleotide metabolism.
“It is established that MYC upregulates glycolysis, DNA-synthesis, and nucleotide metabolism [80]–[82].”
From Gene Expression Analysis of Zebrafish Melanocytes, Iridophores, and Retinal Pigmented Epithelium Reveals Indicators of Biological Function and Developmental Origin (2013) · cites this paper as [80]
The section “Coordinated Regulation of Proteins that Control the Glycolytic Flux” (pp. 7–8) says increased c-MYC activity helps upregulate glycolytic-enzyme genes and glycolytic capacity. Our copy does not say that MYC upregulates DNA synthesis or nucleotide metabolism; searches for those terms found no supporting passage. (LLM, conf=0.87)
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Self-citation
- Authors
- Yeung, S. J., Pan, J., & Lee, M.-H.
- Affiliations
- Sun Yat-sen University (CN)
- The University of Texas MD Anderson Cancer Center (US)
- ORCID
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2008-09-03
- Volume
- 65
- Issue
- 24
- Pages
- 3981-3999
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11131737
- OpenAlex
- W2076767106
- Cited by
- 514
- References
- 6
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 25 · 2023: 27 · 2022: 25 · 2021: 38 · 2020: 37 · 2019: 27 · 2018: 31 · 2017: 41 · 2016: 31 · 2015: 26 · 2014: 33 · 2013: 37 · 2012: 36
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA089266, R56CA089266)
- 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
- p53, c-Myc, HIF-1, glycolysis, Warburg effect, tumor metabolic reprogramming, mitochondrial dysfunction, hypoxia, anaerobic metabolism, intracellular pH, tumor suppressor, oncogenes, energy metabolism, diabetes mellitus
- MeSH terms
- Animals, Glycolysis, Humans, Neoplasms, Tumor Suppressor Protein p53, Proto-Oncogene Proteins c-myc, Hypoxia-Inducible Factor 1, Metabolomics
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