文章基本信息

标题：Transforming Growth Factor Beta Promotes the Expansion of Cancer Stem Cells via S1PR3 by Ligand-Independent Notch Activation
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作者：Naoya Hirata ; Shigeru Yamada ; Shota Yanagida 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2022
卷号：45
期号：5
页码：649-658
DOI：10.1248/bpb.b22-00112
语种：English
出版社：The Pharmaceutical Society of Japan
摘要：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.
关键词：cancer stem cell;Transforming Growth Factor-β (TGFβ);ALK5;sphingosine kinase 1 (SphK1);sphingosine-1-phosphate (S1P);Notch