Autotaxin

Abstract

Autotaxin is a protein of approximately 900 amino acids discovered in the early 1990s. Over the past 15 years, a strong association between cancer cells and autotaxin production has been observed. Recent publications indicate that autotaxin and the capacity of cancer to metastasise are intimately linked. The discovery of new molecular targets in pharmacology is a mixture of pure luck, hard work and industrial strategy. Despite a crucial and desperate need for new therapeutic tools, many targets are approached in oncology, but only a few are validated and end up at the patient bed. Outside the busy domain of kinases, few targets have been discovered that can be useful in treating cancer, particularly metastatic processes. The fortuitous relationship between autotaxin and lysophosphatidic acid renders the results of observations made in the diabetes/obesity context considerably important. The literature provides observations that may aid in redesigning experiments to validate autotaxin as a potential oncology target.

Lysophosphatidic acid generation by pulmonary NKT cell ENPP-2/autotaxin exacerbates hyperoxic lung injury

“…Bronchial epithelial cells as well as inflammatory macrophages showed the highest expression of autotaxin found in the aforementioned BALFs. Genetic depletion of autotaxin in bronchial epithelial cells and bronchial macrophages resulted in decreased disease severity [20]. In our study, we found that not only is ENPP-2 up-regulated in pulmonary NKT cells after hyperoxia, but that the downstream product LPA also increases after hyperoxic injury.…”

“…In the present study, we demonstrated up-regulation of ENPP-2 (autotaxin) on pulmonary NKT cells in response to hyperoxia. Autotaxin shows a broad tissue distribution in adult mice with high mRNA levels in the lung [20]. Increased autotaxin levels have been demonstrated in other disease models and could be found in synovial fluid of arthritis patients as well as human astrocytes following brain injury suggesting its role in inflammation [21].…”

Cellular function and molecular structure of ecto-nucleotidases

“…The multiple biological functions of NPP2 (autotaxin) are now mainly attributed to its phospholipase D activity and include promotion of cancer cell invasion, cell migration, lymphocyte trafficking, and angiogenesis [343][344][345]. A brainspecific variant (PD-Iα/ATXγ) is found almost exclusively on the myelin forming oligodendrocytes of the brain [346].…”

“…The ENPP2 gene contains 27 exons with a considerable number of potential alternative splicing sites. Three different isoforms have been characterized that differ in length and tissue distribution [344,406]. The nomenclature of the isoforms varies between authors [343,344,348,406].…”

“…Three different isoforms have been characterized that differ in length and tissue distribution [344,406]. The nomenclature of the isoforms varies between authors [343,344,348,406]. The largest isoform (ATXm, ATXα), the human melanomaderived autotaxin [403], comprises 915 aa and contains a highly basic insertion in the catalytic domain.…”