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Updated: Jan 7, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Activation of dimerized BRS3-EP3 suppresses melanoma cell migration through coupling Gαs protein
Zeyuan Wang1,2, Lehao Wu1,2, Miao Guo2
1Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Abstract:
The mechanism underlying the crosstalk between Gαq-coupled bombesin receptor subtype-3 (BRS3) and Gαi-coupled E-prostanoid 3 receptor (EP3) remains unknown. Here, we report that BRS3 and EP3 form dimers in the membrane of living HEK-293T cells. BRS3-EP3 dimers switched to couple Gαs protein upon PGE2 stimulation, which provoked cAMP accumulation and enhanced P38 phosphorylation. Quantitative proteomics analysis revealed that the activation of BRS3-EP3 dimers was associated with cell migration. B16 melanoma cell line, which endogenously expresses BRS3 and EP3, was selected to investigate the function of BRS3-EP3 dimers. The results demonstrated that the presence of BRS3 inhibited the migration of B16 melanoma cells upon PGE2 stimulation. Utilizing inhibitors of Gαs and P38, we found that BRS3 interacted with EP3 and switched to couple Gαs protein, causing P38 phosphorylation to inhibit F-actin rearrangement and ultimately suppressed cell migration. Our study reveals the crosstalk between the orphan receptor BRS3 and EP3, and provides a potential novel target for disease treatment.
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