Autotaxin Implication in Cancer Metastasis and Autoimunne Disorders: Functional Implication of Binding Autotaxin to the Cell Surface.

Olivier Peyruchaud,Lou Saier,Raphaël Leblanc

doi:10.3390/cancers12010105

Olivier Peyruchaud, Lou Saier + Show 1 more

Open Access

https://doi.org/10.3390/cancers12010105

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Abstract

Autotaxin (ATX) is an exoenzyme which, due to its unique lysophospholipase D activity, is responsible for the synthesis of lysophosphatidic acid (LPA). ATX activity is responsible for the concentration of LPA in the blood. ATX expression is increased in various types of cancers, including breast cancer, where it promotes metastasis. The expression of ATX is also remarkably increased under inflammatory conditions, particularly in the osteoarticular compartment, where it controls bone erosion. Biological actions of ATX are mediated by LPA. However, the phosphate head group of LPA is highly sensitive to degradation by the action of lipid phosphate phosphatases, resulting in LPA inactivation. This suggests that for efficient action, LPA requires protection, which is potentially achieved through docking to a carrier protein. Interestingly, recent reports suggest that ATX might act as a docking molecule for LPA and also support the concept that binding of ATX to the cell surface through its interaction with adhesive molecules (integrins, heparan sulfate proteoglycans) could facilitate a rapid route of delivering active LPA to its cell surface receptors. This new mechanism offers a new vision of how ATX/LPA works in cancer metastasis and inflammatory bone diseases, paving the way for new therapeutic developments.

Highlights

The name autotaxin (ATX), proposed by Stracke and colleagues in 1992, arose during the characterization of a new potent autocrine motility-stimulating protein produced by human A2058 melanoma cells [1]
LPAcontains is highlya is mediated the the SMB2 domain sensitive to degradation by phospholipases that are extensively represented at cell surfaces and in canonical Arginin-Glycin-Aspartic acid (RGD) integrin-binding motif, site-directed mutagenesis biological liquids
The question of whether ATX/lysophosphatidic acid (LPA) action on osteoclasts relies on the link of ATX to integrin αvβ3 merits specific investigation. All these results suggest that binding of ATX to the cell surface through its interaction with different adhesion molecules could achieve two major objectives

Summary

Introduction

The name autotaxin (ATX), proposed by Stracke and colleagues in 1992, arose during the characterization of a new potent autocrine motility-stimulating protein produced by human A2058 melanoma cells [1]. ATX lysoPLD activity leads to the production of lysophosphatidic acid (LPA) through the degradation of a series of lysophospholipid precursors, of which lysophosphatidylcholine (LPC) is the most abundant in blood [5] (Figure 1). ATX is a multidomain protein with a somatomedin-B (SMB1,2)-like domain, a central phosphodiesterase catalytic domain (PDE), and a C-terminal inactive catalytic nuclease domain (NUC) (Figure 1). LPA exhibits growth factor-like activity due to the activation of a series of six different. Expression of ENPP2, the ATX gene, is regulated by cytokines, growth factors and hormones (Table 2)

G Proteins

Conclusions