The role of the 12(S)-HETE/GPR31/12-HETER axis in cancer and ischemia-reperfusion injury

Biochem Soc Trans. 2019 Apr 30;47(2):743-754. doi: 10.1042/BST20180635. Epub 2019 Mar 22.

Abstract

The G protein-coupled receptors (GPCRs) constitute a large superfamily of seven transmembrane-spanning receptors that are activated by several classes of ligands, including bioactive lipids. GPCRs are attractive therapeutic targets for the treatment of human diseases, as they finely regulate a wide array of cellular functions. In this minireview, we summarized what is currently known about the G protein-coupled receptor GPR31/12-HETER. We highlighted, in particular, its structural similarity with human homologs, the biological functions of its recognized ligand 12(S)-hydroxyeicosatetraenoic acid (HETE), an arachidonic acid metabolite, and the role that GPR31/12-HETER-mediated signals play in cancer cell growth, invasion and metastasis, and in liver ischemia-reperfusion (IR) injury. Recent studies shed light and interest on the 12(S)-HETE/GPR31/12-HETER-activated signaling pathways and functions. The full spectrum of GPR31/12-HETER-mediated biological functions has yet to be characterized. Further studies are needed to identify other potential ligands, i.e. other than 12(S)-HETE. Another important remaining question is whether the multiple 12(S)-HETE-induced biological activities, including its role in diabetes, neurodegeneration, neuroprotection, and platelet function, occur via GPR31/12-HETER and/or involve the activation of other receptor molecules and pathways.

Keywords: G protein-coupled receptors; cancer; ischaemia–reperfusion injury; lipids.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Reperfusion Injury / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • Receptors, G-Protein-Coupled