Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor
Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor
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DOI：
10.1038/35079135
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发表时间：
2001-05-31
期刊：
影响因子：
64.8
通讯作者：
Fujino, M
中科院分区：
文献类型：
--
作者：
Ohtaki, T;Shintani, Y;Fujino, M
转移是癌症患者死亡的一个主要原因，它涉及一个多步骤的过程，包括癌细胞从原发癌中分离出来，侵袭周围组织，通过循环扩散，再侵袭和远处器官的增殖。KiSS-1是一种人类转移抑制基因(1)，它抑制人类黑色素瘤(2)和乳腺癌(3)的转移，而不影响致瘤性。然而，其基因产物和作用机制尚未阐明。在这里，我们发现KiSS-1(参考文献1，4)编码一个由54个氨基酸残基组成的羧基末端酰胺化肽，它是我们从人胎盘中分离出来的一个孤儿G蛋白偶联受体(HOT7T175)的内源性配体，并命名为“Metastin”。Metastin体外抑制hOT7T175转基因CHO细胞的趋化和侵袭，体内抑制hOT7T175转基因的B16-BL6黑色素瘤的肺转移。这些结果提示了KiSS-1可能的作用机制和一种潜在的新治疗方法。
Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene(1), that suppresses metastases of human melanomas(2) and breast carcinomas(3) without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.