Autotaxin, a secreted lysophospholipase D, as a promising therapeutic target in chronic inflammation and cancer. (April 2015)

• Record Type: Journal Article
• Authors: Barbayianni, Efrosini; Kaffe, Eleanna; Aidinis, Vassilis; Kokotos, George
• Is Part Of: Progress in lipid research. Volume 58(2015:Apr.)
• Page Start: 76
• Page End: 96
• Publication Date: 2015-04
• Subjects: ABTS 2, 2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) -- AML acute myeloid leukemia -- ApnA diadenosine polyphosphates -- ATP adenosine-5′-triphosphate -- ATX autotaxin -- BALF bronchoalveolar lavage fluid -- bis-pNPP bis(p-nitrophenyl) phosphate -- BLM bleomycin -- CAM chorioallantoic membrane -- CNS central nervous system -- CRC colorectal cancer -- CSF cerebrospinal fluid -- CTCs circulating tumor cells -- EAE experimental autoimmune encephalomyelitis -- EBV Epstein-Barr virus -- EDTA ethylenediaminetetraacetic acid -- EGF epidermal growth factor -- ENPP ecto-nucleotide pyrophosphatase/phosphodiesterase -- EOC epithelial ovarian cancer -- FRET fluorescence resonance energy transfer -- GBM glioblastoma multiforme -- GC gastric cancer -- GPCR G protein-coupled receptor -- HCC hepatocellular cancer -- HCV hepatitis C virus -- HRP horseradish peroxidase -- HVA homovanillic acid -- ICAM-1 intercellular adhesion molecule-1 -- IPF idiopathic pulmonary fibrosis -- ITD internal tandem duplication -- LC lung cancer -- LEDGF lens epithelium-derived growth factor -- LPA lysophosphatidic acid -- LPARs LPA receptors -- LPE lysophosphatidylethanolamine -- LPI lysophosphatidylinositol -- LPS lysophosphatidylserine -- LSECs liver sinusoidal endothelial cells -- LVD lymphovascular vessel density -- lysoPLD lysophospholipase D -- MCP-1 monocyte chemoattractant protein-1 -- MORFO oligodendrocyte remodeling and focal adhesion organization domain -- MS multiple sclerosis -- MVD microvessel vascular density -- NAD+ nicotinamide adenine dinucleotide -- NCI National Cancer Institute -- NSCLC non-small-cell lung cancer -- NUC nuclease-like -- OPN osteopontin -- PDE phosphodiesterase -- PDGF platelet derived growth factor -- PI3Kγ phosphatidylinositol 3-kinase γ -- pNP-TMP thymidine 5'-monophosphate p-nitrophenyl ester -- POSTN periostin -- RA rheumatoid arthritis -- RAC1 RAS-related C3 botulinum toxin substrate 1 -- ROS reactive oxygen species -- SMB somatomedin B-like -- SFs synovial fluids -- S1P sphingosine 1-phosphate -- SPC sphingosylphosphorylcholine -- TMZ temozolomide -- TNF tumor necrosis factor -- UDP-glucose uridine diphosphate glucose -- UPA urokinase-type plasminogen activator -- VEGF vascular endothelial growth factor; Autotaxin -- Cancer -- Inflammation -- Inhibitors -- Lysophosphatidic acid -- Lysophospholipase D; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipiden; 572.57
• DOI: 10.1016/j.plipres.2015.02.001
• Languages: English
• ISSNs: 0163-7827

Abstract

Abstract: Autotaxin (ATX) is a member of the nucleotide pyrophosphatase/phosphodiesterase family of ectoenzymes that hydrolyzes phosphodiester bonds of various nucleotides. It possesses lysophospholipase D activity, catalyzing the hydrolysis of lysophosphatidylcholine into lysophosphatidic acid (LPA), and it is considered the major LPA-producing enzyme in the circulation. LPA is a bioactive phospholipid with diverse functions in almost every mammalian cell type, which exerts its action through binding to specific G protein-coupled receptors and stimulates various cellular functions, including migration, proliferation and survival. As a consequence, both ATX and LPA have attracted the interest of researchers, in an effort to understand their roles in physiology and pathophysiology. The present review article aims to summarize the existing knowledge as to the implications of ATX in chronic inflammatory diseases and cancer and to highlight the low molecular weight compounds, which have been developed as leads for the discovery of novel medicines to treat inflammatory diseases and cancer.