Description
Autotaxin, also known as ENPP-2, is a secreted glycoprotein which belongs to the ectonucleotide pyrophosphatase/phosphodiesterase (NPP) family [1,2]. Generally, NPPs can hydrolyze phosphates from nucleotides. Autotaxin exhibits the unique lysophospholipase D activity [3]. The mature protein includes two somatomedin-B-like (SMB) cysteine knot domains, a catalytic domain, and an inactive C-terminal nuclease-like domain with an EF-hand-like motif that is important in cell motility, and a region involved in autotaxin secretion [1,4,5]. There are three isoforms identified in mouse and human [6,7]. Most circulating autotaxin is the beta form which contains 863 amino acid. Autotaxin contributes to the predominant extracellular source of the phospholipid LPA (lysophosphatidic acid) from LPC (lysophosphatidylcholine) [8-11]. Autotaxin can also produce minor amounts of sphingosine 1-phosphate and cyclic phosphatidic acid which can antagonize many of the tumorigenic properties of LPA [9,12].
Autotaxin stimulates tumor cell motility and enhances invasion and metastasis. It's upregulated in melanoma, glioblastoma, breast and lung carcinoma, follicular lymphoma and other cancers [2,8,11]. Autotaxin production by adipocytes enhances pre-adipocyte proliferation and may be elevated in obesity [11, 13].
Autotaxin is present in blood, urine, saliva, seminal and cerebrospinal fluids [2, 3]. In addition, plasma autotaxin is cleared by the liver which is elevated in liver disease [3, 14]. Normal serum or plasma autotaxin concentration is reported to be slightly higher in females than in males, and highest in pregnant females [2, 14]