| Project/Area Number |
17K15591
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
Kitamura Hiroshi 東北大学, スマート・エイジング学際重点研究センター, 助教 (20706949)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | NRF2依存性がん / Cdkn2a / 細胞老化 / 恒常的NRF2活性化 / 老化 / p16 / NRF2 / KEAP1 |
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| Outline of Final Research Achievements |
NRF2-addicted cancer cells are malignant solid tumors and NRF2 accumulation is a prognostic marker. However, it remains to be elucidated how NRF2-addicted cancer cells are established. In order to analyze the molecular mechanisms how NRF2-addiction was established, we performed this research, using murine lung cancer model.
From our analyses, it is implied that NRF2 activation in normal cells induces cellular senescence and protect the cells from carcinogenesis, which was not observed after carcinogenesis. Our data implied that recovering the cellular senescence mechanisms in NRF2 addicted cancer cells could cause the regression of NRF2-addicted cancer cell, which might be the therapeutic target for the malignant solid tumors.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性度の高いNRF2依存性がんは、その発生機構が不明であった。しかし、本研究によりCdkn2aなど細胞の老化誘導機構の破綻が、「正常細胞においては発がんシグナルに対して防御的に働き、がん細胞では悪性化に貢献する」といったユニークなNRF2の機能変化を説明可能な一因子である可能性が示された。本研究で示唆されたこのようなメカニズムが、将来的に、NRF2依存性がんの治療標的になりうる可能性が示されたことも、本研究の重要な成果である。
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