| Project/Area Number |
18K06969
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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 49010:Pathological biochemistry-related
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| Research Institution | Showa University |
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Principal Investigator |
Ishikawa Fumihiro 昭和大学, 大学共同利用機関等の部局等, 准教授 (60515667)
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| Co-Investigator(Kenkyū-buntansha) |
森 一憲 昭和大学, 薬学部, 講師 (60349040)
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 足場非依存性増殖 / がん転移 / レドックス / ミトコンドリア / 転移 / 活性酸素種 |
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| Outline of Final Research Achievements |
To accomplish metastasis, cancer cells need to acquire the ability of anchorage-independent growth, which is achieved by escaping from detachment-induced apoptosis (anoikis).
In this study, we examined the role of SUZ12, a polycomb-group protein, in redox regulation during anoikis. First, we found that SUZ12 knockdown increased reactive oxygen species (ROS) in both cytosol and mitochondria under detached conditions, whose effects was prominent in mitochondria. Moreover, anoikis induced by SUZ12 knockdown was inhibited by antioxidant treatment, overexpression of NRF-2 (which plays a role in protection against oxidative stress), or concomitant overexpression of ROS-scavenging enzymes in mitochondria. In accordance with these results, anoikis was completely blocked in caspase-9 knockout cells that are deficient in intrinsic apoptotic pathway via mitochondria. Together, these results suggest that SUZ12 inhibits anoikis by alleviating mitochondrial oxidative stress in cancer cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本課題の成果から、接着喪失にともなうミトコンドリアでの活性酸素種の上昇はアノイキスを促進し、がん細胞ではSUZ12によって抑制的に制御されていることが明らかになった。一方で、SUZ12の発現によって活性酸素種の産生と消去に関わる既知の酵素の遺伝子の発現レベルはいずれも影響を受けなかった。これらの結果は、SUZ12による新規のレドックス制御機構の存在を示唆しており、レドックス生物学をさらに発展させるものである。また、細胞レベルの予備的な結果ではあるが、抗酸化剤の過剰な摂取はSUZ12と同様の効果を示すことが予想され、がんの進展に促進的に働く可能性が示唆された。
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