The Role of Autotaxin and LPA Signalling in Embryonic Development, Pathophysiology and Cancer

Dear colleagues,

Autotaxin (ATX) was first identified as an autocrine motility-stimulating factor, isolated from the supernatant of highly metastatic melanoma cells. Soon after, its cDNA cloning classified ATX as ectonucleotide pyrophosphatase-phosphodiesterase 2 (ENPP2), possessing phosphodiesterase activity in vitro. However, several years later, it was discovered that ATX is identical to the long elusive plasma lysophospholipase D and is now considered responsible for most of the extracellular production of lysophosphatidic acid (LPA). In turn, LPA is a pleiotropic growth factor-like phospholipid, signalling via its G-protein coupled receptors (LPAR1-6) and activating a multitude of cellular signal transduction pathways. The prevailing working hypothesis suggests that ATX-mediated LPA synthesis is likely localized at the cell surface, through the possible interaction of ATX with integrins or other molecules. Overall, any ATX effect will rely on the presence of the appropriate ligands on the cell surface, and the cell membrane expression profile of LPA receptors, that mediate LPA effects, and lipid phospholipases (LPPs), that catabolise LPA. ATX and LPA have been shown to be essential for embryonic development, while their levels were found to be increased in several chronic inflammatory disorders and types of cancer. Genetic and pharmacological studies in mice have confirmed a pathogenetic role for ATX expression and LPA signalling, and thus provided the proof of principle for therapeutic interventions, as exemplified by the ongoing clinical trials for IPF. Contributions to this Special Issue will provide new insights into the mechanism of action of the ATX/LPA axis, deepen our understanding of their biological role in health and disease, and reveal novel therapeutic opportunities.

Dr. Vassilis Aidinis
Guest Editor

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