A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines.

The metabolic phenotype of cancer cells is reflected by the metabolites they consume and by the byproducts they release. Here, we use quantitative, extracellular metabolomic data of the NCI-60 panel and a novel computational method to generate 120 condition-specific cancer cell line metabolic models...

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Autores principales:	Maike K Aurich, Ronan M T Fleming, Ines Thiele
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2017
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fa1b987fe15c4f63b5c4ad46c7bdbee5
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spelling	oai:doaj.org-article:fa1b987fe15c4f63b5c4ad46c7bdbee52021-12-02T19:58:10ZA systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines.1553-734X1553-735810.1371/journal.pcbi.1005698https://doaj.org/article/fa1b987fe15c4f63b5c4ad46c7bdbee52017-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1005698https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The metabolic phenotype of cancer cells is reflected by the metabolites they consume and by the byproducts they release. Here, we use quantitative, extracellular metabolomic data of the NCI-60 panel and a novel computational method to generate 120 condition-specific cancer cell line metabolic models. These condition-specific cancer models used distinct metabolic strategies to generate energy and cofactors. The analysis of the models' capability to deal with environmental perturbations revealed three oxotypes, differing in the range of allowable oxygen uptake rates. Interestingly, models based on metabolomic profiles of melanoma cells were distinguished from other models through their low oxygen uptake rates, which were associated with a glycolytic phenotype. A subset of the melanoma cell models required reductive carboxylation. The analysis of protein and RNA expression levels from the Human Protein Atlas showed that IDH2, which was an essential gene in the melanoma models, but not IDH1 protein, was detected in normal skin cell types and melanoma. Moreover, the von Hippel-Lindau tumor suppressor (VHL) protein, whose loss is associated with non-hypoxic HIF-stabilization, reductive carboxylation, and promotion of glycolysis, was uniformly absent in melanoma. Thus, the experimental data supported the predicted role of IDH2 and the absence of VHL protein supported the glycolytic and low oxygen phenotype predicted for melanoma. Taken together, our approach of integrating extracellular metabolomic data with metabolic modeling and the combination of different network interrogation methods allowed insights into the metabolism of cells.Maike K AurichRonan M T FlemingInes ThielePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 13, Iss 8, p e1005698 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Maike K Aurich Ronan M T Fleming Ines Thiele A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines.
description	The metabolic phenotype of cancer cells is reflected by the metabolites they consume and by the byproducts they release. Here, we use quantitative, extracellular metabolomic data of the NCI-60 panel and a novel computational method to generate 120 condition-specific cancer cell line metabolic models. These condition-specific cancer models used distinct metabolic strategies to generate energy and cofactors. The analysis of the models' capability to deal with environmental perturbations revealed three oxotypes, differing in the range of allowable oxygen uptake rates. Interestingly, models based on metabolomic profiles of melanoma cells were distinguished from other models through their low oxygen uptake rates, which were associated with a glycolytic phenotype. A subset of the melanoma cell models required reductive carboxylation. The analysis of protein and RNA expression levels from the Human Protein Atlas showed that IDH2, which was an essential gene in the melanoma models, but not IDH1 protein, was detected in normal skin cell types and melanoma. Moreover, the von Hippel-Lindau tumor suppressor (VHL) protein, whose loss is associated with non-hypoxic HIF-stabilization, reductive carboxylation, and promotion of glycolysis, was uniformly absent in melanoma. Thus, the experimental data supported the predicted role of IDH2 and the absence of VHL protein supported the glycolytic and low oxygen phenotype predicted for melanoma. Taken together, our approach of integrating extracellular metabolomic data with metabolic modeling and the combination of different network interrogation methods allowed insights into the metabolism of cells.
format	article
author	Maike K Aurich Ronan M T Fleming Ines Thiele
author_facet	Maike K Aurich Ronan M T Fleming Ines Thiele
author_sort	Maike K Aurich
title	A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines.
title_short	A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines.
title_full	A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines.
title_fullStr	A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines.
title_full_unstemmed	A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines.
title_sort	systems approach reveals distinct metabolic strategies among the nci-60 cancer cell lines.
publisher	Public Library of Science (PLoS)
publishDate	2017
url	https://doaj.org/article/fa1b987fe15c4f63b5c4ad46c7bdbee5
work_keys_str_mv	AT maikekaurich asystemsapproachrevealsdistinctmetabolicstrategiesamongthenci60cancercelllines AT ronanmtfleming asystemsapproachrevealsdistinctmetabolicstrategiesamongthenci60cancercelllines AT inesthiele asystemsapproachrevealsdistinctmetabolicstrategiesamongthenci60cancercelllines AT maikekaurich systemsapproachrevealsdistinctmetabolicstrategiesamongthenci60cancercelllines AT ronanmtfleming systemsapproachrevealsdistinctmetabolicstrategiesamongthenci60cancercelllines AT inesthiele systemsapproachrevealsdistinctmetabolicstrategiesamongthenci60cancercelllines
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A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines.

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