| Project/Area Number |
16K09296
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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 | Osaka Medical College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
朝日 通雄 大阪医科大学, 医学部, 教授 (10397614)
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| Research Collaborator |
Takeuchi Toshihisa
Inoue Takuya
Nakagawa Takatoshi
Moriwaki Kazumasa
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | O-GlcNAc修飾 / 胃癌 / 大腸癌 / NF-κB / GSK3β / FBXL2 / ユビキチン化 / O-GlcNAc 修飾 / 糖尿病 / 癌 / FOXM1 / TGF-3β / FOX-M1 / GSK-3β / 糖鎖 |
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| Outline of Final Research Achievements |
Colon cancer was chemically induced in wild type and O-GlcNAc transferase transgenic mice (Ogt-Tg) to examine the effect of O-GlcNAc modification on cancer onset. As a result, the tumor formation was significantly reduced in Ogt-Tg. We found that elevated O-GlcNAc modification of NF-κB was involved in the reduction.
Furthermore, using a gastric cancer cell line, we studied the effect of O-GlcNAc modification on FOX-M1, a transcription factor which was involved in proliferation or metastasis on gastric cancer, showing that O-GlcNAc modification inhibited the degradation of FOXM1. We found that the inhibition was due to O-GlcNAc modification of GSK3β or FBXL2, which were involved in the ubiquitination of FOXM1.
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| Academic Significance and Societal Importance of the Research Achievements |
翻訳後修飾は、生体の機能に重要な役割を演じている。O-GlcNAc修飾はその一つでセリン・スレオニン残基のリン酸化と競合することにより多くの細胞内シグナルを制御している。 胃癌、大腸癌は、糖尿病が危険因子になっているが、糖尿病が癌に影響を与える原因の一つとして糖尿病で増加すると言われているO-GlcNAc修飾の関与が指摘されている。本研究では、癌に関わるO-GlcNAc修飾のターゲット分子としてNF-κB、GSK3β、 FBXL2を同定したが、さらにその詳細を解明することにより、O-GlcNAc修飾をターゲットとした新規癌治療薬の開発に結び付く可能性が期待される。
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