| Project/Area Number |
18K08650
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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 | Saga University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田中 智和 佐賀大学, 医学部, 助教 (60781903)
能城 浩和 佐賀大学, 医学部, 教授 (90301340)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | HIF-1 / ROS / mieap / MALM / MMP-1 / hypoxia / 癌浸潤 / 低酸素 / Mieap / ミトコンドリア休眠 / 低酸素環境 / 活性酸素 / 胃癌 |
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| Outline of Final Research Achievements |
In this study, we used two GC cell lines. 58As9 GC cells increased ROS accumulation and cancer invasion under hypoxia whereas MKN45 cells do not alter invasion or ROS accumulation. 2019:Mieap expression was observed in MKN45, but not in 58As9 cells. We demonstrated mieap plays a central role in controlling ROS production and cancer invasion in GC cells under hypoxia. We reported these evidences in Scientific Reports in 2020. 2020: Using iTRAQ technology, we tried to isolate mitochondria proteins, which is specifically expressed in MKN45, but not in 58As9. However we failed to isolate significant protein. 2021: In this year, we tried to isolate HIF-1 target gene, which is specifically expressed in 58As9 cells and contributes to hypoxia-induced cancer invasion. As a result, we demonstrated MMP-1 expression is a HIF-1 target and essential in hypoxia-induced cancer invasion in 58As9 cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、低酸素環境下にある固形癌では、MALMというミトコンドリア品質管理機構の破綻が契機となり、細胞内にROSが蓄積することで浸潤能が亢進し、癌悪性度を増強することを胃癌細胞株を用いて証明した。さらにmieapがMALM機序には必須な遺伝子であることも立証した。さらにこの低酸素下での胃癌細胞浸潤能亢進には、HIF-1ターゲット遺伝子であるMMP-1の低酸素発現誘導が重要であることも立証した。本研究は、生体内では低酸素環境下に置かれている固形癌の悪性度増強がmieap発現を基軸にしたMALMという新たな機序により惹起されることを初めて立証した。
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