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miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
AKT1 and MYC induce distinctive metabolic fingerprints in human prostate cancer
Carmen Priolo1, Saumyadipta Pyne1, Joshua Rose1
1Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts.
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 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.
Insights
Prostate cancer cells reprogram metabolism based on specific oncogenes. AKT1 activation promotes aerobic glycolysis, while MYC overexpression affects lipid metabolism, offering new diagnostic and therapeutic targets.
Area of Science:
- Oncology
- Metabolomics
- Molecular Biology
Background:
- Cancer cells alter metabolism to sustain growth, but the specific metabolic reprogramming driven by distinct oncogenes in prostate cancer remains unclear.
- Akt and Myc are key oncogenic drivers in prostate cancer, influencing cell growth and survival.
- Understanding oncogene-specific metabolic reprogramming is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate whether different oncogenic drivers (AKT1 and MYC) induce distinct metabolic reprogramming in human prostate tumors.
- To correlate metabolic profiles with specific oncogenic pathways in prostate cancer.
- To identify potential metabolic biomarkers for prostate cancer subtypes.
Main Methods:
- Utilized mass spectrometry-based metabolite profiling on cell lines, transgenic mouse models, and human prostate specimens.
- Compared metabolic profiles of cells and tissues with AKT1 activation versus MYC overexpression.
- Validated key metabolite changes using absolute quantitation assays.
Main Results:
- AKT1 activation was linked to increased aerobic glycolysis metabolites.
- MYC overexpression was associated with dysregulated lipid metabolism.
- Metabolic reprogramming was independent of Gleason grade and pathologic staging.
Conclusions:
- Prostate tumors exhibit distinct metabolic phenotypes driven by specific oncogenes (AKT1 and MYC).
- These findings highlight the link between molecular phenotype and metabolic reprogramming in prostate cancer.
- The study provides a foundation for developing oncogene-specific metabolic diagnostics and targeted therapeutics for prostate cancer.
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