2018 Fiscal Year Final Research Report
The impact of stromal Hic-5 on the tumorigenesis of colorectal cancer through lysyl oxidase induction and stromal remodeling.
| Project/Area Number |
16K10553
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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 |
Digestive surgery
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| Research Institution | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
金山 朱里 昭和大学, 医学部, 准教授 (10338535)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | Hic-5 / 大腸がん / がん関連線維芽細胞 / 細胞外微小環境制御 |
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| Outline of Final Research Achievements |
Carcinoma-associated fibroblasts (CAFs) influence tumor initiation, progression and metastasis within the tumor-associated stroma. This suggests that CAFs would be a potential target for tumor therapy. Here we found that Hydrogen peroxide-inducible clone-5 (Hic-5), also named transforming growth factor beta-1-induced transcript 1 protein (Tgfb1i1), was strongly induced in CAFs found in human colorectal cancer. To clarify the function and significance of Hic-5 in colorectal cancer in vivo, we utilized a mouse model of azoxymethane (AOM)-induced colorectal cancer using Hic-5 deficient mice. Lack of Hic-5 in CAFs completely prevented AOM-induced colorectal cancer development in the colon tissues of mice. Mechanistic investigation revealed that Hic-5 promoted the expression of lysyl oxidase and collagen I in human control counterpart fibroblasts. Taken together, these results demonstrate that Hic-5 in CAFs is responsible for orchestrating or generating a tumor-promoting stroma.
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| Free Research Field |
消化器外科
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| Academic Significance and Societal Importance of the Research Achievements |
大腸癌は近年増加が著しい悪性腫瘍で，従来の治療に加えて予防的なアプローチも重要性を増している．そこで現状の癌細胞そのものをターゲットにした治療概念にとらわれない、新しい治療ターゲット分子が提唱可能になったと考える．
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