2023 Fiscal Year Final Research Report
Mechanism of gastric cancer naturally development in novel glycan deficient mice
| Project/Area Number |
20K09053
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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 |
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| Co-Investigator(Kenkyū-buntansha) |
中山 淳 信州大学, 学術研究院医学系, 教授 (10221459)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 胃癌 / 糖鎖 / 糖転移酵素 / 遺伝子改変マウス |
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| Outline of Final Research Achievements |
To elucidate the mechanism of gastric carcinogenesis in A4gnt knockout (KO) mice, the regulation of IL-11 signaling activation was investigated. Activation of the JAK2―STAT3 pathway and increased gp130 expression were observed in the gastric mucosa of A4gnt KO mice. Analysis of wild-type mouse gastric mucosa and AGS cells suggested that αGlcNAc binds to IL-11 receptors and gp130, thus preventing the formation of the IL-11/IL-11 receptor/gp130 complex and suppressing STAT3 activation. These results suggest that the gastric tumorigenesis naturally development in A4gnt KO mice can be caused by enhanced activity of IL-11―JAK2―STAT3 signaling pathway.
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| Free Research Field |
生化学 糖鎖生物学
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| Academic Significance and Societal Importance of the Research Achievements |
αGlcNAcの欠損による胃分化型癌の発生機構として、発癌シグナルであるIL-11―JAK2―STAT3経路が活性化されることを明らかにした。たった１つの糖の欠損という僅かな変化が原因で胃に生じる顕著な表現型が癌関連シグナルの活性化によるという事実は、糖鎖病理学領域における新知見であり、学術的意義がある。また、これらの結果からαGlcNAcによる癌関連シグナルの抑制は、新たな胃癌の予防、治療法開発への研究基盤になることが期待できる。
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