TY - JOUR
T1 - Transforming Growth Factor Beta Promotes the Expansion of Cancer Stem Cells via S1PR3 by Ligand-Independent Notch Activation
AU - Hirata, Naoya
AU - Yamada, Shigeru
AU - Yanagida, Shota
AU - Ono, Atsushi
AU - Yasuhiko, Yukuto
AU - Kanda, Yasunari
N1 - Funding Information:
Acknowledgments This work was funded by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (#17K19503 and #21H02634 to Y. K.), the Research on Regulatory Harmonization and Evaluation of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics from Japan Agency for Medical Research and Development, AMED (JP21mk0101189 to Y.K.), and a grant from the Smoking Research Foundation (Y.K.).
Publisher Copyright:
© 2022 The Pharmaceutical Society of Japan
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - ALK5
KW - cancer stem cell
KW - Notch
KW - sphingosine kinase 1 (SphK1)
KW - sphingosine-1-phosphate (S1P)
KW - Transforming Growth Factor-β (TGFβ)
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U2 - 10.1248/bpb.b22-00112
DO - 10.1248/bpb.b22-00112
M3 - Article
C2 - 35491169
AN - SCOPUS:85129781223
VL - 45
SP - 649
EP - 658
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
SN - 0918-6158
IS - 5
ER -
