Transforming Growth Factor Beta Promotes the Expansion of Cancer Stem Cells via S1PR3 by Ligand-Independent Notch Activation

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

Research output: Contribution to journalArticlepeer-review

Abstract

Growing evidence suggests that cancer originates from cancer stem cells (CSCs), which can be identified by aldehyde dehydrogenase (ALDH) activity-based flow cytometry. However, the regulation of CSC growth is not fully understood. In the present study, we investigated the effects of Transforming Growth Factor-β (TGFβ) in breast CSC expansion. Stimulation with TGFβ increased the ALDH-positive breast CSC population via the phosphorylation of sphingosine kinase 1 (SphK1), a sphingosine-1-phosphate (S1P)-producing enzyme, and subsequent S1P-mediated S1P receptor 3 (S1PR3) activation. These data suggest that TGFβ promotes breast CSC expansion via the ALK5/SphK1/S1P/S1PR3 signaling pathway. Our findings provide new insights into the role of TGFβ in the regulation of CSCs.

Original languageEnglish
Pages (from-to)649-658
Number of pages10
JournalBiological and Pharmaceutical Bulletin
Volume45
Issue number5
DOIs
Publication statusPublished - May 2022

Keywords

  • ALK5
  • cancer stem cell
  • Notch
  • sphingosine kinase 1 (SphK1)
  • sphingosine-1-phosphate (S1P)
  • Transforming Growth Factor-β (TGFβ)

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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