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2022 Fiscal Year Final Research Report

Regulation of metabolic heterogeneity by asymmetric cell divisions in ALDH1A3-positive cancer stem cells

Research Project

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Project/Area Number 21K20732
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0801:Pharmaceutical sciences and related fields
Research InstitutionTokyo University of Science

Principal Investigator

Tamori Shoma  東京理科大学, 薬学部生命創薬科学科, 助教 (90909483)

Project Period (FY) 2021-08-30 – 2023-03-31
Keywords癌幹細胞 / 非対称分裂 / 代謝不均一性
Outline of Final Research Achievements

This study revealed a part of the mechanism by which metabolic heterogeneity is acquired in cancer cells through the asymmetric division of ALDH1-positive cancer stem cells. Specifically, by genetically modifying the ALDH1A3 gene, we established clones to track ALDH1A3 expression in breast cancer cell lines and conducted analyses. The results suggested that breast cancer cells maintain highly glycolytic cancer stem cells through asymmetric division while generating low-glycolytic non-cancer stem cells. Furthermore, we identified the asymmetric division of ALDH1-positive cancer stem cells in pancreatic cancer cell lines, indicating the possibility of similar mechanisms contributing to heterogeneity acquisition in cancers other than breast cancer.

Free Research Field

癌幹細胞

Academic Significance and Societal Importance of the Research Achievements

本研究は、癌治療において克服すべき重要な課題である癌細胞の代謝不均一性がどのように獲得されるのか、その仕組みの一端を明らかにした。特に、癌幹細胞の非対称分裂制御が代謝不均一性の獲得過程に重要な役割を果たしていることを示した。これにより、遺伝子変異の蓄積に差がない細胞集団からなる癌であっても、異なる性質を持つ癌細胞が生まれる仕組みに関する新たな知見を提供した。これらの知見は、癌の治療抵抗性を克服するための新しいアプローチの開発につながる可能性がある。

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Published: 2024-01-30  

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