FTY720 inhibits expansion of breast cancer stem cells via PP2A activation

Naoya Hirata, Shigeru Yamada, Shota Yanagida, Atsushi Ono, Yasunari Kanda

Research output: Contribution to journalArticlepeer-review

Abstract

Growing evidence suggests that breast cancer originates from a minor population of cancer cells termed cancer stem cells (CSCs), which can be identified by aldehyde dehydrogenase (ALDH) activity-based flow cytometry analysis. However, novel therapeutic drugs for the eradication of CSCs have not been discovered yet. Recently, drug repositioning, which finds new medical uses from existing drugs, has been expected to facilitate drug discovery. We have previously reported that sphingosine kinase 1 (SphK1) induced proliferation of breast CSCs. In the present study, we focused on the immunosuppressive agent FTY720 (also known as fingolimod or Gilenya), since FTY720 is known to be an inhibitor of SphK1. We found that FTY720 blocked both proliferation of ALDH-positive cells and formation of mammospheres. In addition, we showed that FTY720 reduced the expression of stem cell markers such as Oct3/4, Sox2 and Nanog via upregulation of protein phosphatase 2A (PP2A). These results suggest that FTY720 is an effective drug for breast CSCs in vitro.

Original languageEnglish
Article number7259
JournalInternational journal of molecular sciences
Volume22
Issue number14
DOIs
Publication statusPublished - Jul 2 2021

Keywords

  • ALDH
  • Cancer stem cells
  • Drug repositioning
  • FTY720
  • PP2A
  • SphK1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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