Lysophosphatidic acid's role in cancer highlighted by Nature Reviews Cancer

Nature Reviews Cancer reports that lysophosphatidic acid (LPA) is an extracellular signalling lipid produced by autotaxin (ATX/lysoPLD) that affects cell proliferation, migration and survival, and that LPA levels are elevated in malignant effusions such as ovarian cancer ascites.

Nature Reviews Cancer reviews evidence that lysophosphatidic acid (LPA) functions beyond a metabolic intermediate and acts as an extracellular signalling lipid. The article describes how LPA signals through multiple G-protein-coupled receptors, how extracellular LPA is produced mainly by autotaxin (ATX/lysoPLD), and how LPA is inactivated by lipid phosphate phosphohydrolases (LPPs). It notes elevated LPA in malignant effusions and discusses receptor expression, signalling pathways and the potential to target the LPA cascade in cancer. The review also highlights technical discrepancies in plasma measurements and several unanswered questions about receptor specificity and regulation. Key findings: - LPA is an extracellular mediator that activates multiple GPCR pathways to influence proliferation, motility, survival and production of angiogenic factors. - Autotaxin (ATX/lysoPLD) generates extracellular LPA and is linked in the review to tumour invasion, neovascularization and metastasis. - LPA concentrations are consistently high in malignant effusions such as ovarian cancer ascites, while plasma results are inconsistent across studies and may reflect methodological differences. - LPA signalling is opposed by LPP enzymes and the balance of ATX, receptors and LPPs is discussed as relevant to tumour behaviour and as possible points of therapeutic interest. Summary: The review presents LPA as a multifunctional lipid whose actions align with several cancer hallmarks and emphasizes ATX and LPA receptors as focal points for research. It reports consistent elevation of LPA in malignant effusions but notes inconsistent plasma findings and unresolved technical issues. The article identifies open questions about receptor-specific signalling, regulation of ATX, and LPA metabolism. Undetermined at this time.