Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression

Patrick G. Shaw, Raghothama Chaerkady, Tao Wang, Shauna Vasilatos, Yi Huang, Bennett Van Houten, Akhilesh Pandey, Nancy E. Davidson

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere76220
JournalPLoS One
Volume8
Issue number9
DOIs
StatePublished - Sep 27 2013

Fingerprint

breast neoplasms
Proteomics
proteomics
oxidative phosphorylation
Oxidative Phosphorylation
Breast Neoplasms
protein synthesis
neoplasms
Cells
cell lines
glycolysis
Neoplasms
Proteins
Labeling
lactates
Glycolysis
Tumors
Lactic Acid
Cell Line
isotope labeling

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Shaw, P. G., Chaerkady, R., Wang, T., Vasilatos, S., Huang, Y., Van Houten, B., ... Davidson, N. E. (2013). Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression. PLoS One, 8(9), [e76220]. https://doi.org/10.1371/journal.pone.0076220

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.

In: PLoS One, Vol. 8, No. 9, e76220, 27.09.2013.

Research output: Contribution to journalArticle

Shaw, PG, Chaerkady, R, Wang, T, Vasilatos, S, Huang, Y, Van Houten, B, Pandey, A & Davidson, NE 2013, 'Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression', PLoS One, vol. 8, no. 9, e76220. https://doi.org/10.1371/journal.pone.0076220
Shaw PG, Chaerkady R, Wang T, Vasilatos S, Huang Y, Van Houten B et al. Integrated Proteomic and Metabolic Analysis of Breast Cancer Progression. PLoS One. 2013 Sep 27;8(9). e76220. https://doi.org/10.1371/journal.pone.0076220
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. In: PLoS One. 2013 ; Vol. 8, No. 9.
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