title: Metabolomic characterisation of the effects of oncogenic PIK3CA transformation in a breast epithelial cell line.
abstract: Somatic mutations in PIK3CA are frequently found in a number of human cancers, including breast cancer, altering cellular physiology and tumour sensitivity to chemotherapy. This renders PIK3CA an attractive molecular target for early detection and personalised therapy. Using1H Nuclear Magnetic Resonance spectroscopy (NMR) and Gas Chromatography - Mass Spectrometery (GC-MS) together with13C stable isotope-labelled glucose and glutamine as metabolic tracers, we probed the phenotypic changes in metabolism following a single copy knock-in of mutant PIK3CA (H1047R) in the MCF10A cell line, an important cell model for studying oncogenic transformation in breast tissues. We observed effects in several metabolic pathways, including a decrease in glycerophosphocholine level together with increases in glutaminolysis, de novo fatty acid synthesis and pyruvate entry into the tricarboxylic acid cycle. Our findings highlight altered glyceroplipid metabolism and lipogenesis, as key metabolic phenotypes of mutant PIK3CA transformation that are recapitulated in the MCF10A cellular model.
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Chung-Ho E
authors.initials: CE
authors.lastname: Lau
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.|Research School of Physics and Engineering, Department of Applied Mathematics, Australian National University, Canberra, Australia.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Tredwell
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: James K
authors.initials: JK
authors.lastname: Ellis
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Eric W-F
authors.initials: EW
authors.lastname: Lam
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Hector C
authors.initials: HC
authors.lastname: Keun
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002952:Citric Acid Cycle; D058534:Class I Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005997:Glycerylphosphorylcholine / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000032:analysis; D055442:Metabolome; D055432:Metabolomics; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D066244:Proton Magnetic Resonance Spectroscopy; D011773:Pyruvates / Q000378:metabolism
chemical_list: D008055:Lipids; D011773:Pyruvates; D018698:Glutamic Acid; D005997:Glycerylphosphorylcholine; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human