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Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression

One of the most persistent hallmarks of cancer biology is the preference of tumor cells to derive energy through glycolysis as opposed to the more efficient process of oxidative phosphorylation (OXPHOS). However, little is known about the molecular cascades by which oncogenic pathways bring about th...

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Autores principales: Shaw, Patrick G., Chaerkady, Raghothama, Wang, Tao, Vasilatos, Shauna, Huang, Yi, Van Houten, Bennett, Pandey, Akhilesh, Davidson, Nancy E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785415/
https://www.ncbi.nlm.nih.gov/pubmed/24086712
http://dx.doi.org/10.1371/journal.pone.0076220
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author Shaw, Patrick G.
Chaerkady, Raghothama
Wang, Tao
Vasilatos, Shauna
Huang, Yi
Van Houten, Bennett
Pandey, Akhilesh
Davidson, Nancy E.
author_facet Shaw, Patrick G.
Chaerkady, Raghothama
Wang, Tao
Vasilatos, Shauna
Huang, Yi
Van Houten, Bennett
Pandey, Akhilesh
Davidson, Nancy E.
author_sort Shaw, Patrick G.
collection PubMed
description One of the most persistent hallmarks of cancer biology is the preference of tumor cells to derive energy through glycolysis as opposed to the more efficient process of oxidative phosphorylation (OXPHOS). However, little is known about the molecular cascades by which oncogenic pathways bring about this metabolic switch. We carried out a quantitative proteomic and metabolic analysis of the MCF10A derived cell line model of breast cancer progression that includes parental cells and derivatives representing three different tumor grades of Ras-driven cancer with a common genetic background. A SILAC (Stable Isotope Labeling by Amino acids in Cell culture) labeling strategy was used to quantify protein expression in conjunction with subcellular fractionation to measure dynamic subcellular localization in the nucleus, cytosol and mitochondria. Protein expression and localization across cell lines were compared to cellular metabolic rates as a measure of oxidative phosphorylation (OXPHOS), glycolysis and cellular ATP. Investigation of the metabolic capacity of the four cell lines revealed that cellular OXPHOS decreased with breast cancer progression independently of mitochondrial copy number or electron transport chain protein expression. Furthermore, glycolytic lactate secretion did not increase in accordance with cancer progression and decreasing OXPHOS capacity. However, the relative expression and subcellular enrichment of enzymes critical to lactate and pyruvate metabolism supported the observed extracellular acidification profiles. This analysis of metabolic dysfunction in cancer progression integrated with global protein expression and subcellular localization is a novel and useful technique for determining organelle-specific roles of proteins in disease.
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spelling pubmed-37854152013-10-01 Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression Shaw, Patrick G. Chaerkady, Raghothama Wang, Tao Vasilatos, Shauna Huang, Yi Van Houten, Bennett Pandey, Akhilesh Davidson, Nancy E. PLoS One Research Article One of the most persistent hallmarks of cancer biology is the preference of tumor cells to derive energy through glycolysis as opposed to the more efficient process of oxidative phosphorylation (OXPHOS). However, little is known about the molecular cascades by which oncogenic pathways bring about this metabolic switch. We carried out a quantitative proteomic and metabolic analysis of the MCF10A derived cell line model of breast cancer progression that includes parental cells and derivatives representing three different tumor grades of Ras-driven cancer with a common genetic background. A SILAC (Stable Isotope Labeling by Amino acids in Cell culture) labeling strategy was used to quantify protein expression in conjunction with subcellular fractionation to measure dynamic subcellular localization in the nucleus, cytosol and mitochondria. Protein expression and localization across cell lines were compared to cellular metabolic rates as a measure of oxidative phosphorylation (OXPHOS), glycolysis and cellular ATP. Investigation of the metabolic capacity of the four cell lines revealed that cellular OXPHOS decreased with breast cancer progression independently of mitochondrial copy number or electron transport chain protein expression. Furthermore, glycolytic lactate secretion did not increase in accordance with cancer progression and decreasing OXPHOS capacity. However, the relative expression and subcellular enrichment of enzymes critical to lactate and pyruvate metabolism supported the observed extracellular acidification profiles. This analysis of metabolic dysfunction in cancer progression integrated with global protein expression and subcellular localization is a novel and useful technique for determining organelle-specific roles of proteins in disease. Public Library of Science 2013-09-27 /pmc/articles/PMC3785415/ /pubmed/24086712 http://dx.doi.org/10.1371/journal.pone.0076220 Text en © 2013 Shaw et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Shaw, Patrick G.
Chaerkady, Raghothama
Wang, Tao
Vasilatos, Shauna
Huang, Yi
Van Houten, Bennett
Pandey, Akhilesh
Davidson, Nancy E.
Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression
title Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression
title_full Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression
title_fullStr Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression
title_full_unstemmed Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression
title_short Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression
title_sort integrated proteomic and metabolic analysis of breast cancer progression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785415/
https://www.ncbi.nlm.nih.gov/pubmed/24086712
http://dx.doi.org/10.1371/journal.pone.0076220
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