title: Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells.
abstract: 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.
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Christiaan F
authors.initials: CF
authors.lastname: Labuschagne
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Niels J F
authors.initials: NJ
authors.lastname: van den Broek
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Mackay
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK. Electronic address: k.vousden@beatson.gla.ac.uk.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Vousden
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK. Electronic address: o.maddocks@beatson.gla.ac.uk.
authors.forename: Oliver D K
authors.initials: OD
authors.lastname: Maddocks
mesh_terms: D002244:Carbon / Q000378:metabolism*; D048708:Cell Growth Processes / Q000502:physiology; D005998:Glycine / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D053858:Metabolic Networks and Pathways; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D012694:Serine / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D012694:Serine; D002244:Carbon; D005998:Glycine