Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by matrix metalloproteinases

Takahisa Takino, Naohiko Koshikawa, Hisashi Miyamori, Motohiro Tanaka, Takuma Sasaki, Yasunori Okada, Motoharu Seiki, Hiroshi Sato

研究成果: Article

109 引用 (Scopus)

抜粋

A human placenta cDNA library was screened by the expression cloning method for gene products that interact with matrix metalloproteinases (MMPs), and we isolated a cDNA whose product formed a stable complex with pro-MMP-2 and pro-MMP-9. The cDNA encoded the metastasis suppressor gene KiSS-1. KiSS-1 protein was shown to form a complex with pro-MMP. KiSS-1 protein is known to be processed to peptide ligand of a G-protein-coupled receptor (hOT7T175) named metastin, and suppresses metastasis of tumors expressing the receptor. Active MMP-2, MMP-9, MT1-MMP, MT3-MMP and MT5-MMP cleaved the Gly 118-Leu119 peptide bond of not only full-length KiSS-1 protein but also metastin decapeptide. Metastin decapeptide induced formation of focal adhesion and actin stress fibers in cells expressing the receptor, and digestion of metastin decapeptide by MMP abolished its ligand activity. Migration of HT1080 cells expressing hOT7T175 that harbor a high-level MMP activity was only slightly suppressed by either metastin decapeptide or MMP inhibitor BB-94 alone, but the combination of metastin decapeptide and BB-94 showed a synergistic effect in blocking cell migration. We propose that metastin could be used as an antimetastatic agent in combination with MMP inhibitor, or MMP-resistant forms of metastin could be developed and may also be efficacious.

元の言語English
ページ(範囲)4617-4626
ページ数10
ジャーナルOncogene
22
発行部数30
DOI
出版物ステータスPublished - 2003 7 24
外部発表Yes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • これを引用

    Takino, T., Koshikawa, N., Miyamori, H., Tanaka, M., Sasaki, T., Okada, Y., Seiki, M., & Sato, H. (2003). Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by matrix metalloproteinases. Oncogene, 22(30), 4617-4626. https://doi.org/10.1038/sj.onc.1206542