Title:Understanding the Multifaceted Role of Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2) and its Altered Behaviour in Human Diseases
Volume: 15
Issue: 10
Author(s): R. P. Cholia, H. Nayyar, R. Kumar and A. K. Mantha
Affiliation:
Keywords:
ATX, ENPP2, cell proliferation, LPA, LPC, lysophospholipase D.
Abstract: Ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) also known as
Autotaxin, is a secreted lysophospholipase D, which hydrolyzes lysophosphatidylcholine (LPC) into
Lysophosphatidic acid (LPA). LPA is the bioactive product of ENPP2 enzyme, which induces diverse signalling
pathways via six LPA-G-protein coupled receptors (GPCRs). ENPP2 is an essential protein for normal
development and its altered expression is associated with various human diseases. Cellular ENPP2 silencing
results in lethality at the embryonic stage in mice. Initially, it is identified as an autocrine factor in melanoma
cells. Different research groups are currently exploring to understand the multifaceted role of ENPP2 in various
processes such as embryonic and neural development, migration, invasion, differentiation, proliferation,
angiogenesis, and survival. Altered expression of ENPP2 is also associated with various diseases like
inflammation, cancer, fibrosis, rheumatoid arthritis and neural defects. In this article, we have summarized
structural aspects of ENPP2 and biochemical functions associated with its diverse cellular roles in various
human diseases including cancer and Alzheimer’s disease (AD). In addition, keeping in view and advocating
findings, a note on various phytochemicals and synthetic inhibitors, which are currently explored as therapeutic
agents targeting functions of ENPP2 for the treatment of various human diseases is also presented.
