| Project/Area Number |
17H04107
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
Kanda Yasunari 国立医薬品食品衛生研究所, 薬理部, 部長 (70510387)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | がん / がん幹細胞 / 翻訳 / リボソームフットプリント / 次世代シークエンス / ALDH / 乳癌 / 幹細胞 / 自己複製 / 翻訳制御 / 癌幹細胞 / 創薬 / 創薬応用 / リボソーム |
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| Outline of Final Research Achievements |
Cancers are originated from a small population which is called cancer stem cells (CSCs). CSCs can be identified by aldehyde dehydrogenase (ALDH) assay. However, growth regulation of CSCs is not fully understood. In the present study, we examined translational control of CSCs. To explore the genes which translation is upregulated in ALDH-positive cells in breast cancer cell line, we performed ribosome profiling that provides genome-wide maps of protein synthesis by quantifying ribosome-protected mRNA using the deep sequencing. As a result, we determined approximately 1000 translation products in ALDH-positive cells. Especially, we identified gene X in the ALDH-positive cells. Overexpression of gene X induced increase in ALDH-positive cells. Conversely, knockdown of gene X inhibited the ALDH-positive cells. In addition, gene X was enhanced in ALDH-positive cells from patients with breast cancer. These data suggest that gene X plays a role in translational regulation in CSCs.
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| Academic Significance and Societal Importance of the Research Achievements |
乳癌は遺伝子発現などによる分類が確立され、ルミナール型とHER2型は受容体に対する分子標的治療薬が確立しているのに対して、トリプルネガティブ型は有用な分子標的治療薬が開発されておらず予後も悪い。他の癌に比べて罹患年齢も若く、社会的にも重要な課題である。そこで本研究では、癌の源となる癌幹細胞を用いて、翻訳制御の観点から治療薬の標的分子の探索を行った。リボソームフットプリント法を用いて、トリプルネガティブ型乳癌における癌幹細胞の翻訳制御を詳細に解析し、癌幹細胞において翻訳が亢進している因子を新たに同定することに成功した。以上の結果から、翻訳制御に基づき新たな抗癌剤の技術基盤を構築した。
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