The Oncogenic Palmitoyl-Protein Network in Prostate Cancer
Abstract
Molecular studies of cancer cells and tissues have revealed that the basis for malignant tumor formation, growth, and spread is the disruption of normal patterns of gene and protein expression. Although this concept is fundamental to our understanding of cancer, genes and proteins also interact with a wide range of fat (lipid) molecules in a complex metabolic network. Studies of this lipid network have lagged considerably behind those of genetic mutations and signal transduction cascades. However, evidence from laboratory research as well as studies of human patients indicates that lipid metabolism plays a major role in clinical progression of prostate cancer (PCa) and other solid tumors. For example, population studies indicate that obesity is a risk factor for castrate-resistant PCa, and drugs that lower circulating cholesterol appear to reduce the risk of disease progression. Cell culture, animal experiments, and studies of human tumors have identified an enzyme, fatty acid synthase (FASN), as a biochemically relevant protein in PCa. FASN has been described as a "metabolic oncogene," which operates by an unknown mechanism to promote tumor growth. We know that FASN is the source of a class of lipids called long-chain fatty acids. Most of the long-chain fatty acids synthesized by FASN are used to produce cell membranes and to modify proteins through a process called palmitoylation (where the fatty acid palmitate, or a closely related fatty acid, is affixed to proteins). Studies from our laboratory and others indicate that these lipid products of FASN are related to mechanisms by which cholesterol can promote tumor growth and spread. In this project, we will use a sophisticated method of protein analysis, involving mass spectrometry-based proteomics, to identify lipid-modified proteins downstream from FASN.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 31, 2011
- Accession Number
- ADA544483
Entities
People
- Michael R Freeman