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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Tetsuya Ohtaki & Yasushi Shintani & Susumu Honda & Hirokazu Matsumoto & Akira Hori & Kimiko Kanehashi & Yasuko Terao & Satoshi Kumano & Yoshihiro Takatsu & Yasushi Masuda & Yoshihiro Ishibashi & Takuy, 2001. "Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor," Nature, Nature, vol. 411(6837), pages 613-617, May.
    • Handle: RePEc:nat:nature:v:411:y:2001:i:6837:d:10.1038_35079135
    DOI: 10.1038/35079135
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    Cited by:

    1. Atsushi Imai & Rie Yamada & Keigo Yasuda, 2020. "WDR11 Mutations as A Potential Player of Idiopathic Hypogonadotropic Hypogonadism," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 28(3), pages 21661-21665, June.
    2. Zhenxi Li & Xinghai Yang & Ruifeng Fu & Zhipeng Wu & Shengzhao Xu & Jian Jiao & Ming Qian & Long Zhang & Chunbiao Wu & Tianying Xie & Jiqiang Yao & Zhixiang Wu & Wenjun Li & Guoli Ma & Yu You & Yihua , 2024. "Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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