Open Access

ARTICLE

G-Protein-Coupled Estrogen Receptor Enhances the Stemness of Triple-Negative Breast Cancer Cells and Promotes Malignant Characteristics

by Dongliang Zhu^1,*, Jun Yang², Jiaxin Xu³

1 Department of Cell Biology, Nanjing Medical University, Nanjing, 211166, China
2 Department of Laboratory Medicine, Affiliated People’s Hospital, Jiangsu University, Zhenjiang, 212002, China
3 Department of Biomedical Engineering, Nanjing Medical University, Nanjing, 211166, China

* Corresponding Author: Dongliang Zhu. Email:

Oncologie 2022, 24(3), 471-482. https://doi.org/10.32604/oncologie.2022.024062

Received 23 May 2022; Accepted 20 July 2022; Issue published 19 September 2022

Abstract

G-protein coupled estrogen receptor (GPER) is a transmembrane receptor that mediates non-genomic effects of estrogen. This study aimed to investigate the role of GPER in the stemness formation and malignancies in triple negative breast cancer (TNBC) cells. Spheroids of MDA-MB-468 cells were induced by mammosphere culture, and the proportion of the CD44⁺ /CD24^−/low stem cell subpopulation was detected. Malignant characteristics, expression of GPER and stemness-related markers, and tumorigenesis in a xenograft assay were compared between the mammospheres and adherent cultured cells. The impacts of 17β-estradiol (E2) and the GPER-specific antagonist G15 were studied in in vitro assays. The proportion of the CD44⁺ /CD24^−/low subpopulation was increased in the mammospheres of MDA-MB-468 cells, which also showed higher expression of GPER and stemness-related markers than adherent cultured cells. The abilities of spherical colonies to proliferate, invade, and form colonies in soft agar were enhanced. Spherical cells exhibited stronger tumorigenesis ability than adherent cells in the xenograft assay. E2 treatment enhanced tumorigenicity of both adherent and spherical cells. Spherical cells treated with E2 had stronger proliferation, invasion, and colony formation abilities than other groups. Pretreatment with G15 effectively blocked the stimulation by E2. In conclusion, the expression of GPER in TNBC cells is positively related to stemness and malignant features.

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Keywords

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