Autotaxin and LPA Receptor Signaling in Cancer

Lysophosphatidic acid (LPA; monoacyl-glycerol-3-phosphate) is a lipid mediator that functions as a mitogen and motility factor for many cell types. LPA signals through six specific G protein-coupled receptors, named LPA(1-6), which trigger both overlapping and distinct signaling pathways. LPA is produced from extracellular lysophosphatidylcholine by a secreted lysophospholipase D, named autotaxin (ATX), originally identified as an "autocrine motility factor" for tumor cells. ATX-LPA signaling is vital for embryonic development and promotes tumor formation, angiogenesis, and experimental metastasis in mice. Elevated expression of ATX and/or aberrant expression of LPA receptors are found in several human malignancies, while loss of LPA(6) function has been implicated in bladder cancer. In this review, we summarize our present understanding of ATX and LPA receptor signaling in cancer.