Abstract |
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.
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Authors | Shang-Ru Wu, Chen-Hsin Teng, Ya-Ting Tu, Chun-Jung Ko, Tai-Shan Cheng, Shao-Wei Lan, Hsin-Ying Lin, Hsin-Hsien Lin, Hsin-Fang Tu, Pei-Wen Hsiao, Hsiang-Po Huang, Chung-Hsin Chen, Ming-Shyue Lee |
Journal | Scientific reports
(Sci Rep)
Vol. 7
Issue 1
Pg. 15101
(11 08 2017)
ISSN: 2045-2322 [Electronic] England |
PMID | 29118397
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Membrane Glycoproteins
- SPINT2 protein, human
- Serine Proteinase Inhibitors
- Serine Endopeptidases
- matriptase
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Topics |
- Amino Acid Sequence
- Animals
- Cell Line, Tumor
- Cell Movement
- HEK293 Cells
- Humans
- Male
- Membrane Glycoproteins
(chemistry, genetics, metabolism)
- Mice, Inbred BALB C
- Prostatic Neoplasms
(metabolism, pathology)
- Protein Domains
- Proteolysis
- RNA Interference
- Sequence Homology, Amino Acid
- Serine Endopeptidases
(genetics, metabolism)
- Serine Proteinase Inhibitors
(chemistry, genetics, metabolism)
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