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We are analyzing https://www.nature.com/articles/s41467-021-26395-5.

Title:
The impact of physiological metabolite levels on serine uptake, synthesis and utilization in cancer cells | Nature Communications
Description:
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. Cancer cells in culture are often grown in media conditions containing unphysiological metabolite levels. Here, the authors grow cells under physiological metabolite levels to further understand the reliance of cells on serine and find that when grown under these conditions the cells are less sensitive to serine withdrawal.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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  • Science
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Keywords {🔍}

serine, cells, plasmax, fig, dmem, cancer, hypoxanthine, cell, data, levels, article, supplementary, synthesis, glycine, media, google, scholar, cas, atp, proliferation, novo, grown, represented, nature, wells, triplicate, lcms, metabolism, phgdh, intracellular, tumour, blue, growth, increased, measured, exogenous, experiments, amino, conditions, purine, hct, pathway, mdamb, analysis, number, lower, metabolic, mice, source, dld,

Topics {✒️}

nature portfolio privacy policy ecl chemiluminescence kits line-broadening factor lb = 1 hz chenomx library spectra advertising cancer research uk reprints nature 579 nature 493 nature 544 nature 476 nature 508 nature liquid chromatography–mass spectrometry ad libitum access c-prkdcscid il2rgtm1wjl/szj wallonie-bruxelles international grant fully labelled 13c3-15n-serine predesigned primer/probe assay access exogenous formate essential amino-acid implicated research design research funding u-13c-glucose-derived glycine serine/glycine-free plasmax depleted sodium-dependent transporter asc serine/glycine restriction serine/glycine-deprived chow permissions sodium-dependent transporter system ice-cold extraction buffer p53-dependent metabolic remodelling tracing 13c-labelled formate van de voorde de novo synthesis previously published experiment9 thermofisher scientific de novo purine francis crick institute research synthesised de novo reporting summary tracing deuterium-labelled hypoxanthine small cell lung activating transcription factor-4 starved lung cancer development de novo serine serine/glycine free diet

Schema {🗺️}

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         headline:The impact of physiological metabolite levels on serine uptake, synthesis and utilization in cancer cells
         description: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. Cancer cells in culture are often grown in media conditions containing unphysiological metabolite levels. Here, the authors grow cells under physiological metabolite levels to further understand the reliance of cells on serine and find that when grown under these conditions the cells are less sensitive to serine withdrawal.
         datePublished:2021-10-26T00:00:00Z
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      headline:The impact of physiological metabolite levels on serine uptake, synthesis and utilization in cancer cells
      description: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. Cancer cells in culture are often grown in media conditions containing unphysiological metabolite levels. Here, the authors grow cells under physiological metabolite levels to further understand the reliance of cells on serine and find that when grown under these conditions the cells are less sensitive to serine withdrawal.
      datePublished:2021-10-26T00:00:00Z
      dateModified:2021-10-26T00:00:00Z
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         Cancer metabolism
         Cell growth
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         Humanities and Social Sciences
         multidisciplinary
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      name:The Francis Crick Institute, London, UK
      name:The Francis Crick Institute, London, UK
      name:The Francis Crick Institute, London, UK
      name:The Francis Crick Institute, London, UK

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