GPCR48/LGR4 promotes tumorigenesis of prostate cancer via PI3K/Akt signaling pathway.

G-protein-coupled receptor (GPCR) 48, also known as leucine-rich repeat-containing G-protein-coupled receptor (LGR) 4, is an orphan receptor belonging to the GPCR superfamily, which plays an important role in the development of various organs and multiple cancers. However, the function of GPCR48/LGR4 in prostate cancer has not been fully investigated. Herein, GPCR48/LGR4 was overexpressed and silenced in prostate cancer cells via plasmid and shRNA transfection, respectively. The expression of GPCR48/LGR4 in mRNA and protein levels was analyzed using RT-qPCR and Western blotting, respectively. Subsequently, we demonstrated the effects of GPCR48/LGR4 on the migration, invasion, proliferation and apoptosis of prostate cancer cells, including Du145 and PC-3 cells. Next, we investigated the relationship between GPCR48/LGR4 and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway. The results showed that the overexpression of GPCR48/LGR4 was associated with the up-regulation of Akt, a key effector of PI3K/Akt signaling pathway, which meantime up-regulated the expression of mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3β (GSK-3β), while down-regulated forkhead box, class O (FOXO), all of whom are the downstream targets of PI3K/Akt signaling pathway. Hence, the results suggested that GPCR48/LGR4 may regulate prostate cancer cells and tumor growth via the PI3K/Akt signaling pathway and could provide a better therapeutic target for the diagnosis and treatment of prostate cancer.