期刊
CANCER RESEARCH
卷 74, 期 24, 页码 7198-7204出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-14-1490
关键词
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类别
资金
- Nuclea Biomarkers
- Lank Center/Dana-Farber Cancer Institute
- DBT, India
- MoSPI, India
- DST, India [SR/SA/MS: 516/07, 21/04/2008]
- Fondazione Italiana per la Ricerca sul Cancro, Italy
- Prostate Cancer Foundation
- Friends of Dana-Farber fund
- Patrick C. Walsh Prostate Cancer Research Fund Award
- [R01CA131945]
- [P50 CA90381]
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
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 prostatespecific 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 findings show how prostate tumors undergo a metabolic reprogramming that reflects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.
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