Lysophosphatidic Acid Regulation and Roles in Human Prostate Cancer
Abstract
Originally known for its pedestrian role as an intermediate in intracellular lipid metabolism, LPA is now recognized as a potent lipid mediator that evokes growth-factor-like responses and regulates an array of cellular processes related to pathogenesis of cancer. These include stimulating proliferation by increasing cell cycle progression, enhancing cell survival, stimulating motility and inducing tumor cell invasion, and regulating neovascularization. Progress in understanding LPA actions has accelerated with the discovery that it is a ligand of several G protein coupled cell surface receptors (GPCRs), previously identified as members of the endothelial differentiation gene (EDG) family. To date, three LPA receptors have been identified, EDG-2/LPA1, EDG-4/LPA2, and EDG-7/LPA3. The LPA receptors are differentially expressed, coupled to a variety of O-proteins, and thus regulate diverse cellular responses. Intriguingly, expression of LPA receptors correlates with more advanced prostate cancer cell lines and LPA2 and LPA3 are aberrantly expressed in ovarian cancer cells, indicating a potential role in the pathophysiology of cancer. Recently, a fourth LPA receptor was described (LPA4/GPR23/P2Y9), which is distinct from the other LPA receptors. Moreover, LPA has a novel intracellular function as a high- affinity ligand for peroxisome proliferating activating receptor-gamma, a transcription factor that regulates genes controlling energy metabolism.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA423743
Entities
People
- Sarah Spiegel
Organizations
- Virginia Commonwealth University