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Updated: Oct 27, 2025

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
FTY720 Inhibits Expansion of Breast Cancer Stem Cells via PP2A Activation
Naoya Hirata1,2, Shigeru Yamada1,2, Shota Yanagida1,3
1Division of Pharmacology, National Institute of Health Sciences, Kanagawa 210-9501, Japan.
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.
Insights
The drug FTY720 effectively targets breast cancer stem cells (CSCs) by inhibiting their proliferation and stemness. This study highlights FTY720 as a potential therapeutic agent for breast cancer treatment.
Area of Science:
- Oncology
- Cancer Stem Cell Biology
- Pharmacology
Background:
- Breast cancer may originate from cancer stem cells (CSCs), identified by aldehyde dehydrogenase (ALDH) activity.
- Novel therapeutics targeting CSCs are needed for effective breast cancer treatment.
- Drug repositioning offers a promising avenue for discovering new CSC-targeting drugs.
Purpose of the Study:
- To investigate the efficacy of FTY720, an inhibitor of sphingosine kinase 1 (SphK1), against breast cancer stem cells (CSCs).
- To evaluate FTY720's impact on CSC proliferation, mammosphere formation, and stem cell marker expression.
Main Methods:
- Utilized aldehyde dehydrogenase (ALDH) activity-based flow cytometry to identify and analyze CSCs.
- Assessed the effect of FTY720 on CSC proliferation and mammosphere formation in vitro.
- Measured the expression levels of stem cell markers (Oct3/4, Sox2, Nanog) and protein phosphatase 2A (PP2A).
Main Results:
- FTY720 significantly inhibited the proliferation of ALDH-positive breast CSCs.
- FTY720 treatment reduced mammosphere formation, a measure of stem cell self-renewal.
- FTY720 decreased the expression of key stem cell markers by upregulating PP2A.
Conclusions:
- FTY720 demonstrates potent anti-cancer stem cell activity in vitro.
- FTY720 shows potential as a therapeutic drug for targeting breast CSCs.
- The findings support FTY720 as a repositioned drug candidate for breast cancer therapy.
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