Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.

Abstract:

: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, that suppresses metastases of human melanomas and breast carcinomas 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.

journal_name

Nature

journal_title

Nature

authors

Ohtaki T,Shintani Y,Honda S,Matsumoto H,Hori A,Kanehashi K,Terao Y,Kumano S,Takatsu Y,Masuda Y,Ishibashi Y,Watanabe T,Asada M,Yamada T,Suenaga M,Kitada C,Usuki S,Kurokawa T,Onda H,Nishimura O,Fujino M

doi

10.1038/35079135

keywords:

subject

Has Abstract

pub_date

2001-05-31 00:00:00

pages

613-7

issue

6837

eissn

0028-0836

issn

1476-4687

pii

35079135

journal_volume

411

pub_type

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