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[Cancer Research 62, 5399-5404, October 1, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Identification and Characterization of Mouse Metastasis-suppressor KiSS1 and Its G-Protein-coupled Receptor1

Lewis Joe Stafford, Chunzhi Xia, Wenbin Ma, Yi Cai and Mingyao Liu2

Center for Cancer Biology and Nutrition, Alkek Institute of Biosciences and Technology [L. J. S., C. X., W. M., Y. C., M. L.], and Department of Medical Biochemistry and Genetics [M. L.], Texas A&M University System Health Science Center, Houston, Texas 77030

G-protein-coupled receptors receive many different signals to activate different functions such as cellgrowth, proliferation, and migration. KiSS1 is a metastasis suppressor gene that has been shown to inhibit metastasis of human melanomas and breast carcinomas. The human KiSS1 gene encodes a COOH-terminally amidated active peptide, and this peptide is the ligand of a novel G-protein-coupled receptor. However, the mechanism of the antimetastatic actions of KiSS1 and its G-protein-coupled receptor has not been elucidated. In this study, we identified the mouse homologues of the KiSS1 peptide and its G-protein-coupled receptor and characterized the signaling pathways mediated by the activation of the KiSS1 receptor. Although human and mouse KiSS1 proteins share relatively low overall homology (52%), the active peptides (10-amino-acid residues) are highly conserved between mouse and human KiSS1 proteins, varying by only one conserved amino acid [Tyr (Y) to Phe (F)]. Activation of the receptor by KiSS1 peptide leads to the activation of G-protein-activated phospholipase C (PLC-ß), which suggests direct coupling of the KiSS1 peptide to the G{alpha}q-mediate PLC-Ca2+ signaling pathway. Furthermore, activation of the KiSS1 receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis.




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