Roles of HAI-1, a membrane-anchored serine protease inhibitor, in intestinal carcinogenesis through regulating pericellular proteolysis
| Project/Area Number |
15K08311
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | セリンプロテアーゼ / セリンプロテアーゼインヒビター / 腸管発癌 / HAI-1 / PAR-2 |
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| Outline of Final Research Achievements |
Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-bound serine protease inhibitor expressed on epithelial and carcinoma cell surface. We have previously reported that HAI-1 KO mice showed significantly accelerated tumor formation in the intestine. This study aimed to analyze the roles for HAI-1 in intestinal carcinogenesis. To examine whether PAR-2 signaling is responsible for increased tumor formation observed with Hai-1 deficiency in the ApcMin+ model, we generated HAI-1,PAR-2 double KO mice. We observed that concomitant knockout of PAR-2 reduced the formation of intestinal tumors. Moreover, loss of PAR-2 alleviate the activation of NF-kB in the HAI-1 KO intestine. These results suggested that insufficient Hai-1 function induced PAR-2 activation. Excess activation of PAR-2 induces the activation of NF-kB signaling, which may be responsible for increased intestinal tumorigenesis.
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Ghrelin administration suppresses inflammation-associated colorectal carcinogenesis in mice2015
Author(s)
Kawaguchi M, Kanemaru A, Fukushima T, Yamamoto K, Tanaka H, Haruyama Y, Itoh H, Matsumoto N, Kangawa K, Nakazato M, Kataoka H
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Journal Title
Cancer Sci.
Volume: 106
Issue: 9
Pages: 1130-1136
DOI
Related Report
Peer Reviewed / Open Access
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