Journal article
Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression
PloS one, Vol.8(9), pp.e76220-e76220
09/27/2013
DOI: 10.1371/journal.pone.0076220
PMCID: PMC3785415
PMID: 24086712
Abstract
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.
Details
- Title: Subtitle
- Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression
- Creators
- Patrick G. Shaw - University of PittsburghRaghothama Chaerkady - Johns Hopkins University School of MedicineTao Wang - UPMC Hillman Cancer CenterShauna Vasilatos - UPMC Hillman Cancer CenterYi Huang - UPMC Hillman Cancer CenterBennett Van Houten - UPMC Hillman Cancer CenterAkhilesh Pandey - Johns Hopkins University School of MedicineNancy E. Davidson - UPMC Hillman Cancer Center
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.8(9), pp.e76220-e76220
- DOI
- 10.1371/journal.pone.0076220
- PMID
- 24086712
- PMCID
- PMC3785415
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library Science
- Number of pages
- 12
- Grant note
- T32 CA09110; U54 RR 020839 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) HHSN268201000032C / National Heart, Lung and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) U54RR020839 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) T32CA009110 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) U54 GM103250 / NIH roadmap grant for Technology Centers of Networks and Pathways; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Breast Cancer Research Foundation
- Language
- English
- Date published
- 09/27/2013
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984383890002771
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