Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells
Open accessAbstract
Previous work has shown that some cancer cells are highly dependent on serine/glycine uptake for proliferation. Although serine and glycine can be interconverted and either might be used for nucleotide synthesis and one-carbon metabolism, we show that exogenous glycine cannot replace serine to support cancer cell proliferation. Cancer cells selectively consumed exogenous serine, which was converted to intracellular glycine and one-carbon units for building nucleotides. Restriction of exogenous glycine or depletion of the glycine cleavage system did not impede proliferation. In the absence of serine, uptake of exogenous glycine was unable to support nucleotide synthesis. Indeed, higher concentrations of glycine inhibited proliferation. Under these conditions, glycine was converted to serine, a reaction that would deplete the one-carbon pool. Providing one-carbon units by adding formate rescued nucleotide synthesis and growth of glycine-fed cells. We conclude that nucleotide synthesis and cancer cell proliferation are supported by serine--rather than glycine--consumption.
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Removing serine from culture media limits incorporation of one-carbon units into nucleotides and impairs proliferation.
“Removing serine from culture media limits incorporation of one-carbon units into nucleotides and impairs proliferation (Labuschagne et al., 2014).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Labuschagne et al., 2014
Eliminating environmental serine, limiting aspartate synthesis via mitochondrial inhibition, and ablating the mitochondrial folate pathway impair purine biosynthesis.
“For example, eliminating environmental serine, limiting aspartate synthesis via mitochondrial inhibition, and ablating the mitochondrial folate pathway impairs purine biosynthesis (Ducker et al., 2016; Labuschagne et al., 2014; Sullivan et al., 2015).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Labuschagne et al., 2014
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- Authors
- Labuschagne, C. F., van den Broek, N. J. F., Mackay, G. M., Vousden, K. H., & Maddocks, O. D. K.
- Affiliations
- Cancer Research UK Scotland Institute (GB)
- Corresponding author
- Vousden, Karen H.
- Maddocks, Oliver D.K.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 7
- Issue
- 4
- Pages
- 1248-1258
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2000144783
- Cited by
- 576
- References
- 17
- Citations by year
- 2026: 34 · 2025: 37 · 2024: 47 · 2023: 46 · 2022: 64 · 2021: 69 · 2020: 62 · 2019: 48 · 2018: 40 · 2017: 42 · 2016: 44 · 2015: 34 · 2014: 9
- FWCI
- 13.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Cancer Research UK (18274)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- serine, glycine, one-carbon metabolism, tumor cell proliferation, nucleotide synthesis, glycine cleavage system, formate, amino acid metabolism, cancer metabolism
- MeSH terms
- Carbon, Glycine, Humans, Neoplasms, Serine, HCT116 Cells, Cell Growth Processes, Metabolic Networks and Pathways, MCF-7 Cells
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