TAILIEUCHUNG - Báo cáo Y học: Matrilysin (matrix metalloprotease-7) cleaves membrane-bound annexin II and enhances binding of tissue-type plasminogen activator to cancer cell surfaces

Matrilysin (matrix metalloproteinase-7) plays important roles in tumor progression. It was previously found that matrilysin binds to the surface of colon cancer cells to promote their metastatic potential. In this study, we identified annexin II as a novel membrane-bound substrate of matrilysin. Treatment of human colon cancer cell lines with active matrilysin released a 35 kDa annexin II form, which lacked its N-terminal region, into the culture supernatant. The release of the 35 kDa annexin II by matrilysin was significantly enhanced in the presence of serotonin or heparin | ễFEBS Journal Matrilysin matrix metalloprotease-7 cleaves membrane-bound annexin II and enhances binding of tissue-type plasminogen activator to cancer cell surfaces Jun Tsunezumi1 2 Kazuhiro Yamamoto1 Shouichi Higashi1 2 and Kaoru Miyazaki1 2 1 Division of CellBiology Kihara Institute for BiologicalResearch Yokohama City University Japan 2 Graduate Schoolof Integrated Sciences Yokohama City University Japan Keywords annexin II cancer cells matrilysin matrix metalloproteinase plasminogen activator Correspondence K. Miyazaki Division of Cell Biology Kihara Institute for Biological Research Yokohama City University 641-12 Maioka-cho Totsuka-ku Yokohama Kanagawa 244-0813 Japan Fax 81 45 820 1901 Tel 81 45 820 1905 E-mail miyazaki@ Received 9 May 2008 revised 22 July 2008 accepted 30 July 2008 doi Matrilysin matrix metalloproteinase-7 plays important roles in tumor progression. It was previously found that matrilysin binds to the surface of colon cancer cells to promote their metastatic potential. In this study we identified annexin II as a novel membrane-bound substrate of matrilysin. Treatment of human colon cancer cell lines with active matrilysin released a 35 kDa annexin II form which lacked its N-terminal region into the culture supernatant. The release of the 35 kDa annexin II by matrilysin was significantly enhanced in the presence of serotonin or heparin. Matri-lysin hydrolyzed annexin II at the Lys9-Leu10 bond thus dividing the protein into an N-terminal nonapeptide and the C-terminal 35 kDa fragment. Annexin II is known to serve as a cell surface receptor for tissue-type plasminogen activator tPA . Although the matrilysin treatment liberated the 35 kDa fragment of annexin II from the cell surface it significantly increased tPA binding to the cell membrane. A synthetic N-terminal nonapeptide of annexin II bound to tPA more efficiently than intact annexin II. This peptide formed a heterodimer with intact .

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