2016 Fiscal Year Final Research Report
Novel molecular target in colorectal cancer and inflammatory bowel disease
| Project/Area Number |
26460979
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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 |
Gastroenterology
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| Research Institution | Kindai University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
FUJITA Jun 京都大学, 医学研究科, 教授 (50173430)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 大腸癌 / 炎症性腸疾患 / ストレス応答 |
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| Outline of Final Research Achievements |
We analyzed gene expression of colon tissues obtained from 354 patients with IBD and CAC and found that expression of gankyrin was much higher in colonic mucosa of patients with refractory IBD than in those with IBD in remission. Expression of gankyrin was upregulated in inflammatory cells as well as tumor cells in colonic mucosa of patients with CAC. The interaction between ganlyrin and SHP-1 leads to inhibition of STAT3 activation and to enhancement of TNF-alpha and IL-17 in inflammatory cells. We created mice with intestinal epithelial cell-specific gankyrin ablation and deletion of gankyrin in myeloid and epithelial cells. Gankyrin deficiency in myeloid cells reduced the activity of ERK and the expression of stem cell markers, leading to attenuated tumorigenic potential. These findings provide important insights into the pathogenesis of CAC and suggest that gankyrin is a promising target for developing therapeutic and preventive strategies against CAC.
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| Free Research Field |
消化器内科
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