2017 Fiscal Year Final Research Report
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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| 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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| Free Research Field |
実験病理学、分子生物学
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