Systemic analysis of metabolic reprogramming of live cancer stem cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19378
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Institute of Physical and Chemical Research
• 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)
• Project Period (FY): 2016-04-01 – 2018-03-31
• 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

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.

Free Research Field

消化器内科学