Beyond the Warburg effect: How do cancer cells regulate one-carbon metabolism?
Open accessAbstract
Altered metabolism in cancer cells is critical for tumor growth. One of the most notable aspects of this metabolic reprogramming lies in one-carbon metabolism. Cells require one-carbon units for nucleotide synthesis, methylation reactions, and for the generation of reducing cofactors. Therefore, the ability to rewire and fine-tune one-carbon metabolism is essential for the maintenance of cellular homeostasis. In this review, we describe how the major nutrient, energy, and redox sensors of the cell play a significant role in the regulation of flux through one-carbon metabolism to enable cell fate decisions. We will also discuss how dysregulated oncogenic signaling hijacks these regulatory mechanisms to support and sustain high rates of proliferation and cell survival essential for tumor growth.
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Different oncogenes and oncosuppressors have a critical impact on these metabolic pathways.
“Different oncogenes and oncosupressors have a critical impact on these metabolic pathways [20,40,46,47,75,76].”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [40]
One-carbon metabolism supplies cancer cells with nucleotides, SAM, glutathione, some amino acids, etc.
“One-carbon metabolism supplies cancer cells with nucleotides, which limit cell divisions: SAM—the main donor of methyl groups; glutathione—an important factor of redox homeostasis; some amino acids; etc. [40,65].”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [40]
One-carbon metabolism is commonly dysregulated in cancer due to its contribution to core cellular building blocks, epigenetics, post-translational modifications, and redox homeostasis.
“One-carbon metabolism (1CM) is commonly dysregulated in cancer due to its contribution to core cellular building blocks (e.g., purine and pyrimidine nucleotides), epigenetics, post-translational modifications (PTMs), and redox homeostasis, and it is comprised of a complex network of enzymes.”
From A review of small-molecule inhibitors of one-carbon enzymes: SHMT2 and MTHFD2 in the spotlight (2021) · cites this paper as [1]
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- Authors
- Rosenzweig, A., Blenis, J., & Gomes, A. P.
- Affiliations
- Weill Cornell Medicine (US)
- Corresponding author
- Gomes, Ana P.
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2018-08-15
- Volume
- 6
- Pages
- 90-90
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC6103474
- OpenAlex
- W2885427810
- Cited by
- 107
- References
- 57
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 15 · 2023: 19 · 2022: 12 · 2021: 16 · 2020: 21 · 2019: 12
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Susan G. Komen (PDF17481555)
- National Cancer Institute (K99CA218686-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- one-carbon metabolism, Warburg effect, cancer metabolism, metabolic reprogramming, nucleotide synthesis, DNA methylation, redox regulation, nutrient sensing, energy sensing, oncogenic signaling, cell proliferation, cell fate determination, tumor growth
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