Open AccessProgesterone activates GPR126 to promote breast cancer development via the Gi pathway
Author(s) -
Wen-Tao An,
Hui Ju Lin,
Lijuan Ma,
Chao Zhang,
Yuan Zheng,
Qiuxia Cheng,
Chuanshun Ma,
Xiang Wu,
Zihao Zhang,
Ya-Ni Zhong,
Menghui Wang,
Dongfang He,
Zhao Yang,
Lutao Du,
Shiqing Feng,
Chuanxin Wang,
Fan Yang,
Xiao Peng,
Pengju Zhang,
Xiao Yu,
Jin Peng Sun
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2117004119
Subject(s) - mutagenesis , carcinogenesis , in vivo , receptor , hormone , chemistry , cancer research , progesterone receptor , steroid , transmembrane protein , microbiology and biotechnology , breast cancer , biochemistry , biology , cancer , medicine , mutation , gene , genetics , estrogen receptor
Significance The steroid hormone progesterone is highly involved in different physiological–pathophysiological processes, including bone formation and cancer progression. Understanding the working mechanisms, especially identifying the receptors of progesterone hormones, is of great value. In the present study, we identified GPR126 as a membrane receptor for both progesterone and 17-hydroxyprogesterone and triggered its downstream G protein signaling. We further characterized the residues of GPR126 that interact with these two ligands and found that progesterone promoted the progression of a triple-negative breast cancer model through GPR126-dependent Gi-SRC signaling. Therefore, developing antagonists targeting GPR126-Gi may provide an alternative therapeutic option for patients with triple-negative breast cancer.