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2015 Fiscal Year Final Research Report

Regulation of breast cancer stem cells by E3 ubiquitin ligase CHIP and new anti-cancer drug development

Research Project

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Project/Area Number 26670041
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pharmacology in pharmacy
Research InstitutionNational Institute of Health Sciences

Principal Investigator

Kanda Yasunari  国立医薬品食品衛生研究所, 薬理部, 室長 (70510387)

Project Period (FY) 2014-04-01 – 2016-03-31
Keywords乳癌 / 癌幹細胞 / ユビキチンリガーゼ / 薬剤耐性 / 創薬
Outline of Final Research Achievements

Growing evidence suggest that breast cancer is originated form a minor population which is called cancer stem cells (CSCs). However, there is no agent for CSCs. Here, using microarray screening in aldehyde dehydrogenase (ALDH)-positive CSC model, we identified a novel role for a CHIP/Stub1 ubiquitin ligase in breast CSC regulation. Knockdown of CHIP increased ALDH-positive cells in MCF-7 cells. In contrast, overexpression of CHIP reduced ALDH-positive cells. These data suggest that CHIP negatively regulate breast CSCs. We next examined the effect of compounds that increase expression levels of CHIP. The compound decreased the proportion of ALDH-positive cells in MCF-7 cells. Since knockdown of CHIP did not affect the target gene for the stem cell signaling pathway (Notch, Hedgehog, and Wnt), CHIP is considered to regulate other stem cell target. Taken together, our findings suggest a novel target of CHIP in breast CSCs. CHIP might be a target for drug development against breast cancer.

Free Research Field

幹細胞生物学

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Published: 2017-05-10  

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