2016
DOI: 10.7555/jbr.30.20150058
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Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo

Abstract: Extracellular lysophosphatidate (LPA) is a potent bioactive lipid that signals through six G-protein-coupled receptors. This signaling is required for embryogenesis, tissue repair and remodeling processes. LPA is produced from circulating lysophosphatidylcholine by autotaxin (ATX), and is degraded outside cells by a family of three enzymes called the lipid phosphate phosphatases (LPPs). In many pathological conditions, particularly in cancers, LPA concentrations are increased due to high ATX expression and low… Show more

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Cited by 58 publications
(34 citation statements)
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“…These findings present an interesting potential target for anti-metastatic therapy when treating melanoma. Interestingly, LPP1 and LPP3 have been targeted in potential therapies for ovarian cancer ( Tanyi et al, 2003 b ; Benesch et al, 2016 ). However, these therapies aimed to increase LPP expression in order to reduce overall LPA levels, thereby diminishing its pro-tumourigenic effects.…”
Section: Discussionmentioning
confidence: 99%
“…These findings present an interesting potential target for anti-metastatic therapy when treating melanoma. Interestingly, LPP1 and LPP3 have been targeted in potential therapies for ovarian cancer ( Tanyi et al, 2003 b ; Benesch et al, 2016 ). However, these therapies aimed to increase LPP expression in order to reduce overall LPA levels, thereby diminishing its pro-tumourigenic effects.…”
Section: Discussionmentioning
confidence: 99%
“…4B), while there was no correlation with the corresponding LPA species (Fig S1A). No significant changes in the mRNA profile of PLPPs, largely responsible for extracellular LPA degradation [31], were noted ( Fig. 4C), suggesting minor involvement in the regulation of spinal cord LPA levels in EAE.…”
Section: Increased Atx Levels and Deregulated Lipid Homeostasis In Thmentioning
confidence: 93%
“…It is thought that a major portion of LPP activity may be carried out at the cell surface, where they hydrolyze extracellular lysophosphatidic acid or sphingosine-1-P and the resulting products activate intracellular signaling cascades in neighboring cells [16,50]. This ecto-enzymatic activity of LPPs may have a role in embryogenesis, tissue repair, development of atherosclerosis, and tumor growth and metastasis [51,52]. At intracellular membranes, LPPs have the potential to hydrolyze lipid substrates on the luminal side of ER or Golgi membranes, whereas lipin PAP activity acts at the cytosolic surface of these membranes.…”
Section: Activity and Regulation Of Mammalian Lipin Proteinsmentioning
confidence: 99%