Establishment of the eradication strategy for cancer stem cells by targeting IRF2

Research Project

Project/Area Number	25460061
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Biological pharmacy
Research Institution	Tokyo Medical and Dental University
Principal Investigator	Sato Taku 東京医科歯科大学, 難治疾患研究所, 非常勤講師 (40375259)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000) Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	組織幹細胞 / 癌幹細胞 / サイトカイン
Outline of Final Research Achievements	In order to cure cancer, it is necessary to eliminate cancer stem cells (CSCs), that is resistant to chemotherapy and radiotherapy in a tumor tissue. Hair follicle stem cells (HFSCs) are cell of origin of cancer in mouse skin cancer model. Interferon regulartory factor 2 (IRF-2) is transcriptional factor which negatively regulate IFN signaling in a cell. In this study, I found that the functional decline of HFSCs was induced by direct and/or indirect effect of physiologic IFNs in vivo in IRF2 deficient mice. Furthermore, based on comprehensive gene expression analysis and lineage tracing experiment, chronic IFN exposure induces “aberrant differentiation” on HFSCs. These effects of IFN may applicable for the strategy to eradicate CSCs.