Autotaxin's conversion of LPC to LPA increases motility.

Aserendipitous discovery by Umezu-Goto et al., whose report appears on page 227, links two previously unrelated fields of study and suggests a new avenue of research for developing cancer therapies. The authors sought to study the production of lysophosphatidic acid (LPA), a lipid mediator with multiple biological functions that acts through G-protein–coupled receptors. LPA is produced in plasma from lysophosphatidylcholine (LPC) in a reaction catalyzed by the enzyme lysophospholipase D (lysoPLD), but the gene for lysoPLD had not been identified.

After biochemically purifying lysoPLD from fetal bovine serum, Umezu-Goto et al. discovered that the enzyme is identical to autotaxin, an enzyme associated with melanoma cells. Autotaxin was known to stimulate motility in tumor cells, but its mechanism of action was unclear. The new work shows that autotaxin/lysoPLD stimulates motility and proliferation in multiple cancer cell lines, apparently by producing LPA. In the microenvironment of a tumor, LPC secreted by tumor cells or available in the plasma could encounter autotaxin/lysoPLD released by the tumor cells, leading to the production of LPA and the stimulation of tumor growth and migration. Interfering with this signaling loop might be a promising strategy for cancer treatment. ▪