G protein-coupled receptors (GPCRs) represent the most successful protein family as drug targets. Their roles in the pathogenesis and progression of cancer are attracting more and more attention. However, endogenous ligands of orphan GPCRs have yet to be identified and their physiological actions remain elusive.

　　GPR160 belongs to class A GPCR family. As an orphan receptor, its structure and function are still unknown. Research groups led by Drs. WANG Mingwei and DING Jian of the National Center for Drug Screening, Shanghai Institute of Materia Medica of Chinese Academy of Sciences collaboratively elucidated functions orphan GPCRs.

　　The researchers found that the transcription level of GPR160 in certain prostate cancer cell lines and tissue samples was significantly higher than that seen in normal prostate cell and tissues. Knockdown of GPR160 resulted in apoptosis and growth arrest of prostate cancer cells both in vitro and in athymic mice. The differential expression pattern of genes was compared with GeneChip in cells infected with scramble or GPR160-targeting shRNA lentiviruses. Gene ontology and network analyses of differentially expressed genes suggested the potential of GPR160 being a cytokine receptor. Treatment of cells with GPR160-targeting shRNA lentiviruses or duplex siRNA oligos markedly elevated the transcription of IL6 and CASP1 genes. A caspase1 selective inhibitor partially rescued cell apoptosis induced by GPR160 knockdown.

　　Prostate cancer is currently the most commonly diagnosed non-dermatologic malignancy among males. Its incidence is increasing in recent years especially for advanced stage prostate cancer with poor survival rate. There is an urgent medical need for developing new therapeutic agents to combat this disease.

　　This research was headed by Associate Professor ZHOU Caihong and was published online in Oncotarget. It reports the correlation of GPR160 with prostate cancer for the first time, thereby offering the opportunity of discovering novel therapies for prostate cancer targeting GPR160.

　　The work was partially supported by grants from the National Health and Family Planning Commission of China, Chinese Academy of Sciences and Shanghai Science and Technology Commission.