Cholesterol and prostate cancer
- 27 October 2003
- journal article
- review article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 91 (1), 54-69
- https://doi.org/10.1002/jcb.10724
Abstract
Cholesterol is a neutral lipid that accumulates in liquid‐ordered, detergent‐resistant membrane domains called lipid rafts. Lipid rafts serve as membrane platforms for signal transduction mechanisms that mediate cell growth, survival, and a variety of other processes relevant to cancer. A number of studies, going back many years, demonstrate that cholesterol accumulates in solid tumors and that cholesterol homeostasis breaks down in the prostate with aging and with the transition to the malignant state. This review summarizes the established links between cholesterol and prostate cancer (PCa), with a focus on how accumulation of cholesterol within the lipid raft component of the plasma membrane may stimulate signaling pathways that promote progression to hormone refractory disease. We propose that increases in cholesterol in prostate tumor cell membranes, resulting from increases in circulating levels or from dysregulation of endogenous synthesis, results in the coalescence of raft domains. This would have the effect of sequestering positive regulators of oncogenic signaling within rafts, while maintaining negative regulators in the liquid‐disordered membrane fraction. This approach toward examining the function of lipid rafts in prostate cancer cells may provide insight into the role of circulating cholesterol in malignant growth and on the potential relationship between diet and aggressive disease. Large‐scale characterization of proteins that localize to cholesterol‐rich domains may help unveil signaling networks and pathways that will lead to identification of new biomarkers for disease progression and potentially to novel targets for therapeutic intervention.Keywords
This publication has 115 references indexed in Scilit:
- Unbiased quantitative proteomics of lipid rafts reveals high specificity for signaling factorsProceedings of the National Academy of Sciences of the United States of America, 2003
- Essential Role of Caveolae in Interleukin-6- and Insulin-like Growth Factor I-triggered Akt-1-mediated Survival of Multiple Myeloma CellsPublished by Elsevier BV ,2003
- Partitioning of Lipid-Modified Monomeric GFPs into Membrane Microdomains of Live CellsScience, 2002
- Cholesterol Depletion Disrupts Caveolae and Insulin Receptor Signaling for Metabolic Control via Insulin Receptor Substrate-1, but Not for Mitogen-activated Protein Kinase ControlPublished by Elsevier BV ,2001
- Interaction of a Receptor Tyrosine Kinase, EGF-R, with Caveolins: CAVEOLIN BINDING NEGATIVELY REGULATES TYROSINE AND SERINE/THREONINE KINASE ACTIVITIESPublished by Elsevier BV ,1997
- Influence of dietary levels of fat, cholesterol, and calcium on colorectal cancerNutrition and Cancer, 1997
- Low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels are coordinately reduced in human renal cell carcinomaBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1996
- Effects of testosterone on cholesterol levels and fatty acid composition in the ratLife Sciences, 1993
- Caveolin, a protein component of caveolae membrane coatsCell, 1992
- Tissue-selective inhibition of cholesterol synthesis in vivo by pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitorBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1990