Unraveling the working principle of MEK inhibitor resistance in cancer cells by artificial control of cell growth signal dynamics
| Project/Area Number |
16K21109
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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 |
Tumor biology
Cell biology
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Komatsu Naoki 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (30737440)
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| Project Period (FY) |
2016-04-01 – 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 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | mTORC1 / 細胞周期 / 細胞増殖 / MEK阻害剤抵抗性 / 蛍光ライブイメージング / 光遺伝学 / 生物画像解析 / 生細胞イメージング / mTOR / MEK阻害剤 / 抗癌剤抵抗性 / 蛍光プローブ / 光操作 / 細胞内シグナル伝達 / シグナル伝達 |
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| Outline of Final Research Achievements |
It remains largely elusive that how cancer cells show intrinsic resistance to MEK inhibitors. To understand the essentials of the resistance in cancer cells, this study aimed to unravel the working principle of the MEK inhibitor resistance from the viewpoint of activity dynamics of cell growth signaling. For this purpose, I established an imaging system for simultaneous monitoring of the dynamics of mTORC1 activity and that of cell cycle progression in living cells. An image analysis pipeline for the obtained images was also developed. The analysis pipeline enabled to track cell cycle statuses from single cell for more than 3 days with quantitative manner. I also examined the possibilities of manipulating mTORC1 activity dynamics with higher temporal resolution. During the analysis, I obtained a preliminary data that implies a novel regulatory mechanism of mTORC1 activity via homo-multimerization of mTOR.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞周期の時系列変化を1細胞レベルかつ数日間にわたって定量的に追跡できるようになったことで、今後は細胞増殖に限らず細胞分化や細胞死といった、細胞周期が関わる多くの生命現象に関する理解を一層加速することが期待される。mTORのホモ多量体化によるmTORC1活性制御の分子機構が今後解明されることで、新しい機序に基づくmTORC1活性の制御法が開発される可能性がある。そのような方法はmTORC1標的治療法の新規の候補になり得ると考えられる。
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] A platform of BRET-FRET hybrid biosensors for optogenetics, chemical screening, and in vivo imaging.2018
Author(s)
Komatsu N, Terai K, Imanishi A, Kamioka Y, Sumiyama K, Jin T, Okada Y, Nagai T, Matsuda M.
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 8984-8984
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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