@article{dbbc9473bf714793a01dad476416ca86,
title = "The impact of physiological metabolite levels on serine uptake, synthesis and utilization in cancer cells",
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.",
author = "Marc Hennequart and Labuschagne, {Christiaan F.} and Myl{\`e}ne Tajan and Pilley, {Steven E.} and Cheung, {Eric C.} and Legrave, {Nathalie M.} and Driscoll, {Paul C.} and Vousden, {Karen H.}",
note = "Funding Information: Metabolomic analysis was supported by Dr. James Macrae and the metabolomics STP of the Francis Crick Institute and through provision of access to the MRC Biomedical NMR Centre. The work was funded by Cancer Research UK grant C596/A26855 and supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001557 and FC001029), the UK Medical Research Council (FC001557 and FC001029) and the Wellcome Trust (FC001557 and FC001029). MH is in receipt of a Wallonie-Bruxelles International Grant of Excellence WBI.WORLD (SUB/2019/441394). Funding Information: KHV is on the Board of Directors and shareholder of Bristol Myers Squibb and on the Science Advisory Board (with stock options) of PMV Pharma, RAZE Therapeutics and Volastra Therapeutics. She is also on the SAB of Ludwig Cancer. KHV is a co-founder and consultant of Faeth Therapeutics, funded by Khosla Ventures. She has been in receipt of research funding from Astex Pharmaceuticals and AstraZeneca and contributed to CRUK Cancer Research Technology filing of Patent Application WO/2017/ 144877. All other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "1",
doi = "10.1038/s41467-021-26395-5",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
