Elucidation of the mechanism of cellular competition mediated by autophagy-related proteins
| Project/Area Number |
18K08016
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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 53010:Gastroenterology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
稲見 義宏 順天堂大学, 医学部, 准教授 (70445500)
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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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 細胞競合 / オートファジー / p62 / 癌治療 / カテプシンL / 癌 |
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| Outline of Final Research Achievements |
In liver cancer, hepatocellular carcinoma cells with p62 aggregates are observed in about 70%. We found that p62, autophagy-specific substrate, plays a pivotal role on triggering cell competition. A cell competition phenomenon is confirmed in which p62-deficient cells phagocyte the p62-accumulated cells. It was found that winner cells in this cell competition strongly express mRNA and protein that induce resistance to low nutrition environment, oxidative stress, and endoplasmic reticulum stress. In addition, it is possible to reduce the total number of tumor cells by co-culturing p62-deficient winner cells with drug-induced cell death gene and p62-accumulating cells. It was suggested that new anti-cancer treatment using cell competition may be useful as a new treatment for cancer cells with accumulation of p62.
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| Academic Significance and Societal Importance of the Research Achievements |
薬物治療の進歩によってB型肝炎やC型肝炎などウイルス性肝炎からの肝癌が減少すると考えられている一方で、脂肪肝やアルコール性肝炎など生活習慣に関連した肝硬変・肝癌は増加すると予測されている。肝癌は難治であり死亡率は日本における全がん死の中で５番目に多い。本研究のような肝癌の特性に着目した新たな抗癌治療の開発は学術的にも社会的にも意義があると思われる。
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Report
(4 results)
Research Products
(1 results)
