Targeting Lysophosphatidic Acid Signaling in Breast Cancer Cells

摘要

Autotaxin (ATX) is a tumor cell-derived enzyme that regulates cancer cell growth motility and survival. ATX exhibits both phosphodiesterase and lysophospholipase D (lysoPLD) catalytic activities. The lysoPLp activity of ATX has been reported to generate lysophosphatidic (LPA) acid via hydrolysis of lysophosphatylcholine substrate. IJPA exerts its effects on target cells primarily through the actions at G-protein coupled cell surface receptors. Because the actions of ATX on cancer cells are very similar to those elicited by LPA, the biological activity of ATX has been suggested to result from the - production of LPA by the hydrolysis of lysoglycerophospholipid substrates that are produced by cells or present in cell culture systems. The broad purpose of the proposed research is to investigate the effects of IJPA signaling in breast cancer cells. Specifically by targeting an important enzyme involved in the extracellular production of this bioactive lipid mediator. The long-term goal of the particular research presented in this report is to define the regulation, mechanism and biological significance of the lysophopholipase D activity of ATX.