AKT1 and MYC induce distinctive metabolic fingerprints in human prostate cancer

Carmen Priolo, Saumyadipta Pyne, Joshua Rose, Erzsébet Ravasz Regan, Giorgia Zadra, Cornelia Photopoulos, Stefano Cacciatore, Denise Schultz, Natalia Scaglia, Jonathan McDunn, Angelo M. De Marzo, Massimo Loda

Research output: Contribution to journalArticle

Abstract

Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry-based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostate-specific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our fi ndings show how prostate tumors undergo a metabolic reprogramming that refl ects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.

Original languageEnglish (US)
Pages (from-to)7198-7204
Number of pages7
JournalCancer Research
Volume74
Issue number24
DOIs
StatePublished - Dec 15 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Priolo, C., Pyne, S., Rose, J., Regan, E. R., Zadra, G., Photopoulos, C., Cacciatore, S., Schultz, D., Scaglia, N., McDunn, J., De Marzo, A. M., & Loda, M. (2014). AKT1 and MYC induce distinctive metabolic fingerprints in human prostate cancer. Cancer Research, 74(24), 7198-7204. https://doi.org/10.1158/0008-5472.CAN-14-1490