GPER-induced signaling is essential for the survival of breast cancer stem cells.

Abstract:

: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.

journal_name

Int J Cancer

authors

Chan YT,Lai AC,Lin RJ,Wang YH,Wang YT,Chang WW,Wu HY,Lin YJ,Chang WY,Wu JC,Yu JC,Chen YJ,Yu AL

doi

10.1002/ijc.32588

subject

Has Abstract

pub_date

2020-03-15 00:00:00

pages

1674-1685

issue

6

eissn

0020-7136

issn

1097-0215

journal_volume

146

pub_type

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