Autotaxin, a secreted lysophospholipase D, as a promising therapeutic target in chronic inflammation and cancer

Prog Lipid Res. 2015 Apr;58:76-96. doi: 10.1016/j.plipres.2015.02.001. Epub 2015 Feb 20.

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.

Keywords: Autotaxin; Cancer; Inflammation; Inhibitors; Lysophosphatidic acid; Lysophospholipase D.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / therapeutic use*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Chronic Disease
  • Embryonic Development
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Phosphoric Diester Hydrolases / chemistry
  • Phosphoric Diester Hydrolases / metabolism*
  • Substrate Specificity

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Phosphoric Diester Hydrolases
  • alkylglycerophosphoethanolamine phosphodiesterase