The Oncogenic Palmitoyl-Protein Network in Prostate Cancer
Annual progress rept. 1 Mar 2012-28 Feb 2013
CEDARS-SINAI MEDICAL CENTER LOS ANGELES CA
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Epidemiological data indicate that cholesterol-lowering pharmacotherapy, primarily HMG-CoA-reductase inhibitors status, reduce the risk Of aggressive prostate cancer PCs. The FDA-approved anti-obesity drug, Orlistat, which inhibits the enzyme fatty acid Synthase FASN, has been shown to slow the growth of human prostate tumors in mice. Despite these advances, studies of lipid metabolism in PCa have lagged behind other areas of research on cell signaling, and limited information is available about how these promising preclinical and clinical data might be leveraged to improve patient outcomes. Our hypothesis is that PCa progression is dependent on a Palmitoyl-protein network regulated by FASN. We predict that the activity of this network can be suppressed by reducing levels of circulating cholesterol. Specific Aims We will challenge this hypothesis with the following specific aims Aim 1 Identify critical Palmitoyl-proteins in the FASN subnetwork. Test their functional roles. Aim 2 Determine whether the FASN-dependent Palmitoyl network can be suppressed in vivo by cholesterol reduction. This project is uncovering new information of potential relevance to 1 dietary influences on PCa risk, and 2 the role of cholesterol and other membrane lipids in PCa progression.
- Anatomy and Physiology
- Medicine and Medical Research