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

Tetsuya Ohtaki (), Yasushi Shintani, Susumu Honda, Hirokazu Matsumoto, Akira Hori, Kimiko Kanehashi, Yasuko Terao, Satoshi Kumano, Yoshihiro Takatsu, Yasushi Masuda, Yoshihiro Ishibashi, Takuya Watanabe, Mari Asada, Takao Yamada, Masato Suenaga, Chieko Kitada, Satoshi Usuki, Tsutomu Kurokawa, Haruo Onda, Osamu Nishimura and Masahiko Fujino
Additional contact information
Tetsuya Ohtaki: Takeda Chemical Industries Ltd
Yasushi Shintani: Takeda Chemical Industries Ltd
Susumu Honda: Takeda Chemical Industries Ltd
Hirokazu Matsumoto: Takeda Chemical Industries Ltd
Akira Hori: Takeda Chemical Industries Ltd
Kimiko Kanehashi: Takeda Chemical Industries Ltd
Yasuko Terao: Takeda Chemical Industries Ltd
Satoshi Kumano: Takeda Chemical Industries Ltd
Yoshihiro Takatsu: Takeda Chemical Industries Ltd
Yasushi Masuda: Takeda Chemical Industries Ltd
Yoshihiro Ishibashi: Takeda Chemical Industries Ltd
Takuya Watanabe: Takeda Chemical Industries Ltd
Mari Asada: Takeda Chemical Industries Ltd
Takao Yamada: Takeda Chemical Industries Ltd
Masato Suenaga: Takeda Chemical Industries Ltd
Chieko Kitada: Takeda Chemical Industries Ltd
Satoshi Usuki: Institute of Clinical Medicine, University of Tsukuba
Tsutomu Kurokawa: Takeda Chemical Industries Ltd
Haruo Onda: Takeda Chemical Industries Ltd
Osamu Nishimura: Takeda Chemical Industries Ltd
Masahiko Fujino: Takeda Chemical Industries Ltd

Nature, 2001, vol. 411, issue 6837, 613-617

Abstract: 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 gene1, that suppresses metastases of human melanomas2 and breast carcinomas3 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.

Date: 2001
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DOI: 10.1038/35079135

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