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The impact of physiological metabolite levels on serine uptake, synthesis and utilization in cancer cells

Marc Hennequart, Christiaan F. Labuschagne, Mylène Tajan, Steven E. Pilley, Eric C. Cheung, Nathalie M. Legrave, Paul C. Driscoll and Karen H. Vousden ()
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Marc Hennequart: The Francis Crick Institute
Christiaan F. Labuschagne: The Francis Crick Institute
Mylène Tajan: The Francis Crick Institute
Steven E. Pilley: The Francis Crick Institute
Eric C. Cheung: The Francis Crick Institute
Nathalie M. Legrave: The Francis Crick Institute
Paul C. Driscoll: The Francis Crick Institute
Karen H. Vousden: The Francis Crick Institute

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract Serine is a non-essential amino acid that is critical for tumour proliferation and depletion of circulating serine results in reduced tumour growth and increased survival in various cancer models. While many cancer cells cultured in a standard tissue culture medium depend on exogenous serine for optimal growth, here we report that these cells are less sensitive to serine/glycine depletion in medium containing physiological levels of metabolites. The lower requirement for exogenous serine under these culture conditions reflects both increased de novo serine synthesis and the use of hypoxanthine (not present in the standard medium) to support purine synthesis. Limiting serine availability leads to increased uptake of extracellular hypoxanthine, sparing available serine for other pathways such as glutathione synthesis. Taken together these results improve our understanding of serine metabolism in physiologically relevant nutrient conditions and allow us to predict interventions that may enhance the therapeutic response to dietary serine/glycine limitation.

Date: 2021
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DOI: 10.1038/s41467-021-26395-5

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