https://scholars.lib.ntu.edu.tw/handle/123456789/454720
標題: | The Kunitz Domain i of Hepatocyte Growth Factor Activator Inhibitor-2 Inhibits Matriptase Activity and Invasive Ability of Human Prostate Cancer Cells | 作者: | Wu S.-R. Teng C.-H. Tu Y.-T. Chun-Jung Ko Cheng T.-S. Lan S.-W. Lin H.-Y. Lin H.-H. Tu H.-F. Hsiao P.-W. HSIANG-PO HUANG CHUNG-HSIN CHEN MING-SHYUE LEE |
公開日期: | 2017 | 出版社: | Nature Publishing Group | 卷: | 7 | 期: | 1 | 來源出版物: | Scientific Reports | 摘要: | Dysregulation of pericellular proteolysis is often required for tumor invasion and cancer progression. It has been shown that down-regulation of hepatocyte growth factor activator inhibitor-2 (HAI-2) results in activation of matriptase (a membrane-anchored serine protease), human prostate cancer cell motility and tumor growth. In this study, we further characterized if HAI-2 was a cognate inhibitor for matriptase and identified which Kunitz domain of HAI-2 was required for inhibiting matriptase and human prostate cancer cell motility. Our results show that HAI-2 overexpression suppressed matriptase-induced prostate cancer cell motility. We demonstrate that HAI-2 interacts with matriptase on cell surface and inhibits matriptase proteolytic activity. Moreover, cellular HAI-2 harnesses its Kunitz domain 1 (KD1) to inhibit matriptase activation and prostate cancer cell motility although recombinant KD1 and KD2 of HAI-2 both show an inhibitory activity and interaction with matriptase protease domain. The results together indicate that HAI-2 is a cognate inhibitor of matriptase, and KD1 of HAI-2 plays a major role in the inhibition of cellular matritptase activation as well as human prostate cancer invasion. ? 2017 The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85033370838&doi=10.1038%2fs41598-017-15415-4&partnerID=40&md5=5c55d7fcf304872f4bc352d0bf3b1e82 https://scholars.lib.ntu.edu.tw/handle/123456789/454720 |
ISSN: | 2045-2322 | DOI: | 10.1038/s41598-017-15415-4 | SDG/關鍵字: | matriptase; membrane protein; serine proteinase; serine proteinase inhibitor; SPINT2 protein, human; amino acid sequence; animal; Bagg albino mouse; cell motion; chemistry; genetics; HEK293 cell line; human; male; metabolism; pathology; prostate tumor; protein degradation; protein domain; RNA interference; sequence homology; tumor cell line; Amino Acid Sequence; Animals; Cell Line, Tumor; Cell Movement; HEK293 Cells; Humans; Male; Membrane Glycoproteins; Mice, Inbred BALB C; Prostatic Neoplasms; Protein Domains; Proteolysis; RNA Interference; Sequence Homology, Amino Acid; Serine Endopeptidases; Serine Proteinase Inhibitors |
顯示於: | 生物化學暨分子生物學科研究所 |
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