Journal
CANCERS
Volume 12, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/cancers12010105
Keywords
autotaxin; lysophosphatidic acid; integrins; heparan sulfate; platelets; metastasis; inflammation; osteoclast; T cells
Categories
Funding
- INSERM
- Universite Claude Bernard Lyon 1
- Comite Departemental de la Savoie de la Ligue Contre le Cancer
- French Foundation pour la Recherche sur le Cancer (ARC) [PJA20151203151]
- ANR grant LYSBONE [ANR-15-CE14-0010-01]
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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.
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