Overexpression of ovarian cancer G-protein-coupled receptor 1 (OGR1) in prostate cancer cell induces apoptosis and inhibits cell migration

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Prostate cancer is the second leading cause of cancer-related deaths in men in the United States. Ovarian cancer G-protein-couple-receptor 1 (OGR1) is a high affinity receptor for sphingosylphosphorylcholine (SPC), a bioactive lipid. A number of observations have suggested that OGR1 is a potential tumor suppressor gene. OGR1 is not expressed in normal ovary, prostate, colon, liver skeletal muscle or pancreas. However, OGR1 was cloned from an ovarian cancer cell line, and it is expressed in a prostate cancer cell line, PC3. Previously, it had been shown that OGR1 mediates SPC-induced MAP kinase activation and growth inhibition in HEK293 cells. We show here that OGR1 overexpression in highly apoptosis resistant and metastatic human PC3 prostate cancer cells induces apoptosis as assessed by PAPR cleavage and annexin V flow cytometry analysis. We also present evidence that OGR1 inhibits cell migration to extracellular matrix proteins, such as vitronectin and osteopontin. The presence of its ligand, SPC, enhances the inhibitory effect of OGR1 on cell migration. OGR1 overexpression in PC3 also inhibits phosphorylation of the serine/threonine protein kinase PKB (Akt), which is a key mediator of cell survival and death. The Akt pathway (which is constitutively active in most prostate cancer) is a therapeutic target in prostate cancer therapy. The inhibitory effect of OGR1 overexpression on Akt phosphorylation in PC3 was enhanced by SPC treatment in a dose- and time- dependent manner. Our findings suggest that OGR1 and its ligand, SPC can be used for developing a therapeutic strategy for prostate cancer therapy.