The path of GPR87: from a P2Y-like receptor to its role in cancer progression

GPR87 is a G protein-coupled seven-transmembrane receptor first described as an orphan receptor in 2001. Despite its high structural homology to several extracellular nucleotide-activated P2Y receptors and sharing conserved sequence motifs in transmembrane regions, identification of endogenous ligands from the class of nucleotides and their analogues has failed for GPR87. Although lysophosphatidic acid was proposed to be a natural ligand for this cell surface receptor, these data are preliminary and inconsistent, and IUPHAR is currently considering GPR87 as an orphan receptor. Thus, the endogenous ligands and physiological functions of GPR87 are still required to be determined and/or confirmed. The remarkably higher expression of GPR87 in human malignant tissues compared to the normal healthy ones clearly suggests that this receptor may be involved in the development and progression of cancerous neoplasms. Therefore, in this review article, the main focus is placed on the oncogenic role of GPR87 in various human malignancies, presenting it as a potential novel target site for therapeutic interventions using both humanized monoclonal antibodies and gene therapy but also selective antagonists which are still waiting for their identification. Furthermore, the importance of the expression of GPR87 as a predictive biomarker for evaluating the prognosis and overall survival of cancer patients is also highlighted.