| Project/Area Number |
18K08613
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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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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Shinshu University |
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Principal Investigator |
Fujii Chifumi 信州大学, 学術研究院医学系, 助教 (10361982)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 分化型胃がん / 細胞増殖 / 浸潤 / αGlcNAc / MUC1 / PODXL / 分化型胃癌 / 腺粘液糖鎖 / 胃がん |
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| Outline of Final Research Achievements |
Gastric gland mucin harbors unique O-glycans carrying terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). α1,4-N-acethlglucosaminyltransferase (α4GnT) is the sole enzyme for αGlcNAc biosynthesis. We established α4GnT-expressing AGS cells, a differentiated gastric cancer cell line, using Tet-On system (AGS-A), and analyzed the effects on cancer cell phenotypes. We found that in vitro cell proliferation, invasion, and tumorigenicity of αGlcNAc-positive cells were significantly suppressed compared with control cells. To clarify the molecular mechanism of above phenotypes, we identified 2 novel αGlcNAc-binding proteins, MUC1 and podocalyxin-like protein 1, in AGS-A cells. Galectin-3 binding to MUC1-N terminus region and phosphorylation to MUC1-C terminus region were attenuated by αGlcNAc synthesis in AGS-A cells. These results suggest that αGlcNAc regulates cancer cell phenotypes by modulating MUC1 signal transduction.
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| Academic Significance and Societal Importance of the Research Achievements |
αGlcNAcは、がんの悪性化に従いその産生量が低下することが報告されているが、その意義は不明であった。本研究の成果は、がん細胞にαGlcNAcを産生させると悪性度が低下することを示すものである。この際にがん細胞でαGlcNAcが結合する新規タンパク質2種を同定し、MUC１へのαGlcNAcの結合が、がん細胞の悪性化を制御する分子機構についても明らかにした。これらの新たな知見の学術的意義は非常に高いと考えられる。またαGlcNAcの産生量低下が、がん細胞の悪性度を制御していることを機能的に示すことができたため、αGlcNAcが、がんの診断マーカーとしても有用であることを示唆している。
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