| Project/Area Number |
18K14700
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2018: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
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| Keywords | 細胞接着 / 細胞運動 / シグナル伝達 / 細胞骨格 / 集団細胞運動 / カドヘリン接着 |
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| Outline of Final Research Achievements |
Collective cell migration underlies many physiological and pathological processes. The aim of this study was to elucidate the mechanisms that regulate collective cell migration by focusing on the cell adhesion machinery, specifically α-catenin, which undergoes a structural change in response to mechanical stress.
We found that the conformational activation of α-catenin occurred anisotropically at the cell junctions of collectively migrating cells. RhoA activity was elevated and F-actin and myosin accumulation at cell junctions was enhanced in cells expressing constitutively altered α-catenin; collective cell migration was slowed in these cells due to a lack of directional cohesion among neighboring cells. We also showed that the establishment of anisotropic force distribution at cell junctions regulates stable directional alignment of multiple cells during collective cell movement by mathematical modeling and simulation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、力の情報を介した細胞集団のコミュニケーション機構が生化学的シグナルとどのように統合され、細胞集団運動を発揮するのかという重要な未解決課題に着目している。そして、細胞接着の質的・量的変化が、細胞集団において不均衡な張力分布をもたらすことを明らかにした。本研究の成果は新しいがんの浸潤・転移に対する新たな予防法や治療法の確立につながることが期待できる。加えて、上皮細胞シートの協調的な運動メカニズムの解明は、創傷治癒応答の遷延化によっておこる褥瘡などの疾患に対する新たな予防法や治療法を開発する上で基礎となる知見である。
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