L-α-lysophosphatidylinositol meets GPR55: a deadly relationship

Trends Pharmacol Sci. 2011 May;32(5):265-9. doi: 10.1016/j.tips.2011.01.005. Epub 2011 Mar 1.

Abstract

Evidence points to a role of L-α-lysophosphatidylinositol (LPI) in cancer. First, clinical data identified LPI as a biomarker for poor prognosis in cancer patients. Second, in vitro studies demonstrated significantly elevated levels of LPI in highly proliferative cancer cells. Third, LPI displays mitogenic activity in cancer cell lines, in which the lipid significantly increased cell proliferation. However, a receptor target for LPI remained elusive until very recently. It has now been revealed that LPI activates GPR55, a G protein-coupled receptor that couples to G(12/13) and G(q) proteins, which direct oncogenic signalling. New evidence indicates that LPI and GPR55 are key partners in driving cancer cell proliferation and migration. GPR55 is expressed in human tumours and drives proliferation and its expression correlates with tumour aggressiveness. Overall patient survival is lower in patients whose glioblastomas express higher levels of GPR55. Thus, evidence suggests that interaction with GPR55 might underlie the pro-tumoural actions of LPI.

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Cell Movement
  • Cell Proliferation
  • Glioblastoma / physiopathology
  • Humans
  • Lysophospholipids / metabolism*
  • Neoplasms / physiopathology*
  • Receptors, Cannabinoid
  • Receptors, G-Protein-Coupled / metabolism*
  • Survival

Substances

  • Biomarkers, Tumor
  • GPR55 protein, human
  • Lysophospholipids
  • Receptors, Cannabinoid
  • Receptors, G-Protein-Coupled
  • lysophosphatidylinositol