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.
Original language | English |
---|---|
Article number | 46079 |
Journal | Scientific Reports |
Volume | 7 |
DOIs | |
Publication status | Published - 10 Apr 2017 |
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Lau, C. H. E., Tredwell, G. D., Ellis, J. K., Lam, E. W. F., & Keun, H. C. (2017). Metabolomic characterisation of the effects of oncogenic PIK3CA transformation in a breast epithelial cell line. Scientific Reports, 7, Article 46079. https://doi.org/10.1038/srep46079
Lau, Chung Ho E. ; Tredwell, Gregory D. ; Ellis, James K. et al. / Metabolomic characterisation of the effects of oncogenic PIK3CA transformation in a breast epithelial cell line. In: Scientific Reports. 2017 ; Vol. 7.
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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. 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.",
author = "Lau, {Chung Ho E.} and Tredwell, {Gregory D.} and Ellis, {James K.} and Lam, {Eric W.F.} and Keun, {Hector C.}",
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Lau, CHE, Tredwell, GD, Ellis, JK, Lam, EWF & Keun, HC 2017, 'Metabolomic characterisation of the effects of oncogenic PIK3CA transformation in a breast epithelial cell line', Scientific Reports, vol. 7, 46079. https://doi.org/10.1038/srep46079
Metabolomic characterisation of the effects of oncogenic PIK3CA transformation in a breast epithelial cell line. / Lau, Chung Ho E.; Tredwell, Gregory D.; Ellis, James K. et al.
In: Scientific Reports, Vol. 7, 46079, 10.04.2017.
Research output: Contribution to journal › Article › peer-review
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T1 - Metabolomic characterisation of the effects of oncogenic PIK3CA transformation in a breast epithelial cell line
AU - Lau, Chung Ho E.
AU - Tredwell, Gregory D.
AU - Ellis, James K.
AU - Lam, Eric W.F.
AU - Keun, Hector C.
N1 - Publisher Copyright:© The Author(s) 2017.
PY - 2017/4/10
Y1 - 2017/4/10
N2 - 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.
AB - 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.
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Lau CHE, Tredwell GD, Ellis JK, Lam EWF, Keun HC. Metabolomic characterisation of the effects of oncogenic PIK3CA transformation in a breast epithelial cell line. Scientific Reports. 2017 Apr 10;7:46079. doi: 10.1038/srep46079