| Project/Area Number |
15H04696
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Chubu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大海 雄介 中部大学, 生命健康科学部, 助手 (10584758)
山内 祥生 名古屋大学, 医学系研究科, 講師 (00444878)
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| Co-Investigator(Renkei-kenkyūsha) |
OHKAWA Yuki 中部大学, 生命健康科学部, 研究員 (40723896)
ANDO Hiromune 岐阜大学, 応用生物科学部, 教授 (20372518)
SUZUKI Kenichi 京都大学, 工学部, 准教授 (50423059)
IKEDA Kazutaka 独立行政法人理化学研究所, 生命医科学研究センター, 上級研究員 (10466732)
HONKE Koichi 高知大学, 医歯学系, 教授 (80190263)
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | シグレック / スフィンゴ糖脂質 / セラミド / 脂肪酸 / ガングリオシド / 脂質修飾 / シグナル制御 / 糖鎖 / シグナル伝達 / 癌 / 生体分子 / 糖脂質 / ノックアウト / 脂質 / シグナル |
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| Outline of Final Research Achievements |
To investigate the mechanisms for signal regulation by glycosphingolipids expressed on the cell surface, chemical structures of whole molecules of glycolipids including sugar moieties and lipid portions were analyzed. Using sugar-remodeling cancer cells and EMARS/MS, we identified membrane molecules that associate with glycolipids, and verified that these molecules specifically bind with glycolipids, and enhance malignant properties of cancer cells. On the other hand, to clarify the involvement of lipid portions in the signal regulation by glycolipids, we performed knockout of DES2 that hydroxylates long chain base-C4 using GD3-expressing colon cancer, DLD-1, and demonstrated the recovery of the reactivity with Siglec-7. We also performed knockout of FA2H that exerts hydroxylation of fatty acid C2, and verified that binding of Siglec-7 is disturbed by hydroxylation of lipid portions. Furthermore, we observed that the sensitivity of cells to NK was increased in the knockout cells.
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