GPER‐induced signaling is essential for the survival of breast cancer stem cells
In: International Journal of Cancer, Jg. 146 (2020-03-15), Heft 6
Online
academicJournal
- 1674 - 1685
G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER- /PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.
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GPER‐induced signaling is essential for the survival of breast cancer stem cells
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Autor/in / Beteiligte Person: | Chan, Yu‐Tzu ; Lai, Alan C‐Y ; Lin, Ruey‐Jen ; Wang, Ya‐Hui ; Wang, Yi‐Ting ; Chang, Wen‐Wei ; Wu, Hsin‐Yi ; Lin, Yu‐Ju ; Chang, Wen‐Ying ; Wu, Jen‐Chine ; Yu, Jyh‐Cherng ; Chen, Yu‐Ju ; Yu, Alice L |
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Zeitschrift: | International Journal of Cancer, Jg. 146 (2020-03-15), Heft 6 |
Veröffentlichung: | eScholarship, University of California, 2020 |
Medientyp: | academicJournal |
Umfang: | 1674 - 1685 |
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