Systemic analysis of metabolic reprogramming of live cancer stem cells
| Project/Area Number |
16K19378
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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 |
Gastroenterology
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Qin Xian-Yang 国立研究開発法人理化学研究所, ライフサイエンス技術基盤研究センター, 特別研究員 (60756815)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 不飽和脂肪酸 / がん幹細胞 / 肝発がん / MYCN / オミクス解析 / 酸化ストレス / 肝癌 / 癌幹細胞 / 化学予防 / 癌 / 細胞・組織 / 発生・分化 / 脂質 / シグナル伝達 |
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| Outline of Final Research Achievements |
Acyclic retinoid (ACR) is a synthetic vitamin A-like compound capable of preventing the recurrence of hepatocellular carcinoma (HCC). I performed omics analyses to identify molecular targets of ACR. In vivo metabolome analysis revealed that inhibition of biosynthesis of unsaturated fatty acids such as arachidonic acid (AA) but not glucose metabolism played a crucial role in the prevention of hepatic tumorigenesis by ACR. In vitro mechanical analysis showed a critical role of induced ROS/TG2 signaling in liver injury by AA. A genome-wide transcriptome analysis identified that an MYCN+EpCAM+ cancer stem cell (CSC)-like subpopulation was selectively depleted by ACR. Further proteome/metabolome analyses showed unsaturated fatty acids were enriched in EpCAM+ CSC-like HCC cells compared with EpCAM- cells. These findings suggested a potential role of unsaturated fatty acid-associated metabolic changes during hepatic tumorigenesis, which might serve as a therapeutic target for HCC prevention.
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid2018
Author(s)
Qin XY, Suzuki H, Honda M, Okada H, Kaneko S, Inoue I, Ebisui E, Hashimoto K, Carninci P, Kanki K, Tatsukawa H, Ishibashi N, Masaki T, Matsuura T, Kagechika H, Toriguchi K, Hatano E, Shirakami Y, Shiota G, Shimizu M, Moriwaki H, Kojima S
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Journal Title
Proc Natl Acad Sci U S A
Volume: 115
Issue: 19
Pages: 4969-4974
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Hepatic orosomucoid is an additional essential regulator promoting hepatocyte proliferation during liver regeneration2016
Author(s)
Xian-Yang Qin, Mitsuko Hara, Erik Arner, Yoshikuni Kawaguchi, Norihiro Kokudo, Harukazu Suzuki, Piero Carninci, Alistair Forrest, Soichi Kojima
Organizer
AASLD2016 第67回米国肝臓学会議
Place of Presentation
John B. Hynes Veterans Memorial Convention Center (Boston, MA, USA)
Year and Date
2016-11-11
Related Report
Int'l Joint Research
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