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Metabolomic characterisation of the effects of oncogenic PIK3CA transformation in a breast epithelial cell line

Title: Metabolomic characterisation of the effects of oncogenic PIK3CA transformation in a breast epithelial cell line
Authors: Lau, C-HE
Tredwell, GD
Ellis, JK
Lam, EW-F
Keun, HC
Item Type: Journal Article
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. Using 1H Nuclear Magnetic Resonance spectroscopy (NMR) and Gas Chromatography – Mass Spectrometery (GC-MS) together with 13C 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.
Issue Date: 10-Apr-2017
Date of Acceptance: 10-Mar-2017
URI: http://hdl.handle.net/10044/1/48205
DOI: https://dx.doi.org/10.1038/srep46079
ISSN: 2045-2322
Publisher: NATURE PUBLISHING GROUP
Journal / Book Title: SCIENTIFIC REPORTS
Volume: 7
Copyright Statement: © 2017 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MR/N012097/1
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CHOLINE PHOSPHOLIPID-METABOLISM
PYRUVATE-DEHYDROGENASE
AEROBIC GLYCOLYSIS
CLINICAL-TRIALS
CANCER-CELLS
FATTY-ACIDS
PATHWAY
INSULIN
GLUCOSE
KINASE
Publication Status: Published
Article Number: ARTN 46079
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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