Journal article

Kisspeptin-10-induced signaling of GPR54 negatively regulates chemotactic responses mediated by CXCB4: a potential mechanism for the metastasis suppressor activity of kisspeptins

JM Navenot, ZX Wang, N Chopin, N Fujii, SC Peiper

Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2005


The product of the KiSS-1 gene is absent or expressed at low level in metastatic melanoma and breast cancer compared with their nonmetastatic counterparts. A polypeptide derived from the KiSS-1 product, designated kisspeptin-10 (Kp-10), activates a receptor coupled to Galphaq subunits (GPR54 or KiSS-1R). To study the mechanism by which Kp-10 antagonizes metastatic spread, the effect on CXCR4-mediated signaling, which has been shown to direct organ-specific migration of tumor cells, was determined. Kp-10 blocked chemotaxis of tumor cells expressing CXCR4 in response to low and high concentrations of SDF-1/CXCL12 and inhibited mobilization of calcium ions induced by this ligand. Pretreatment w..

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