2021 Fiscal Year Final Research Report
Analysis of the molecular basis of atypical cell-death induction with vacuolar formation in cancer cells by CDK4/6 inhibitors
| Project/Area Number |
18K15031
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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 48030:Pharmacology-related
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| Research Institution | Nihon University (2019-2021)
Tokyo Medical University (2018) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | abemaciclib / CDK4/6 / 自食胞形成 / 細胞死 / リソソーム / オートリソソーム |
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| Outline of Final Research Achievements |
CDK4/6 inhibitor abemaciclib, which is used as anticancer drug, induces large vacuole formation in cytosol and causes cell death. In this study, we revealed that these large vacuoles induced by abemaciclib are swelling autolysosome. The vacuolar formation is independent of ATG5-related autophagy and is linked to cell death. It was also suggested that CDK4,6, main target of abemaciclib, functions as a target at least in part in the induction of vacuolar formation by abemaciclib. From these results, a part of mechanism in inducing large vacuolar formation in cytosol and in causing cell death is revealed.
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| Free Research Field |
生化学、細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は抗がん剤として使用されているCDK4/6阻害薬による自食胞形成を伴った細胞死の誘導に着目し、CDK4/6による新規の細胞死様式を解明することを目指したものである。これらで得られる知見は、将来的にCDK4/6阻害薬と併用する薬剤の選択や適用の拡大、副作用の防止等の観点からも重要なものである。さらに、CDK4/6阻害薬abemaciclibによる自食胞形成は本来のCDK4/6のターゲットとは異なる標的分子にも作用した結果である可能性もあり、これまで想定されていたCDK4/6阻害薬の作用機序とは異なる、新たな作用機序の提唱に繋がると期待される。
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