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Serine, glycine and one-carbon units: cancer metabolism in full circle

Nature Reviews Cancer volume 13, pages 572–583 (2013)Cite this article

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Key Points

  • One-carbon metabolism integrates cellular nutrient status by cycling carbon units from amino acid inputs to generate diverse outputs, including redox maintenance and cellular biosynthesis.

  • The epigenetic status of cells also seems to be directly linked to one-carbon metabolism through protein and nucleic acid methylation.

  • One-carbon metabolism has long been the focus of antimetabolite-based chemotherapy that includes the agents methotrexate and 5-fluorouracil — two of the most widely used chemotherapies. Additional therapies are currently being explored.

  • Recent findings have provided genetic and functional evidence that multiple nodes in the pathway contain candidate driver genes for oncogenesis.

  • Additional research in one-carbon metabolism may provide biomarkers that would enable advances in patient selection for antimetabolite chemotherapy.

Abstract

One-carbon metabolism involving the folate and methionine cycles integrates nutritional status from amino acids, glucose and vitamins, and generates diverse outputs, such as the biosynthesis of lipids, nucleotides and proteins, the maintenance of redox status and the substrates for methylation reactions. Long considered a 'housekeeping' process, this pathway has recently been shown to have additional complexity. Genetic and functional evidence suggests that hyperactivation of this pathway is a driver of oncogenesis and establishes a link to cellular epigenetic status. Given the wealth of clinically available agents that target one-carbon metabolism, these new findings could present opportunities for translation into precision cancer medicine.

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Figure 1: (Timeline): One-carbon metabolism in cancer
Figure 2: One-carbon metabolism is an integrator of nutrient status.
Figure 3: Folate and methionine metabolism constitute one-carbon metabolism.
Figure 4: Nutrients that fuel one-carbon metabolism.
Figure 5: One-carbon metabolism, cancer pathology and intervention.

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Acknowledgements

The author is grateful to members of his laboratory for helpful discussions. He also thanks L. Cantley for stimulating conversations in this area and the anonymous reviewers for their helpful comments. The work was supported through funding from the American Cancer Society and the US National Cancer Institute (CA168997).

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  1. Field of Biochemistry and Molecular Cell Biology, Cornell University, Ithaca, 14850, New York, USA

    Jason W. Locasale

  2. Field of Genomics, Genetics and Development, Cornell University, Ithaca, 14850, New York, USA

    Jason W. Locasale

  3. Tri-Institutional Program in Computational Biology and Medicine, Cornell University, Weill Cornell Medical College, and Memorial Sloan Kettering Cancer Institute, Cornell University, Ithaca, 14850, New York, USA

    Jason W. Locasale

  4. Divison of Nutritional Sciences, Cornell University, Ithaca, 14850, New York, USA

    Jason W. Locasale

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Locasale, J. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer 13, 572–583 (2013). https://doi.org/10.1038/nrc3557

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