1. Estrogen regulates Hippo signaling via GPER in breast cancer
- Author
-
Zhou, Xin, Wang, Shuyang, Wang, Zhen, Feng, Xu, Liu, Peng, Lv, Xian-Bo, Li, Fulong, Yu, Fa-Xing, Sun, Yiping, Yuan, Haixin, Zhu, Hongguang, Xiong, Yue, Lei, Qun-Ying, and Guan, Kun-Liang
- Subjects
Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biological Sciences ,Genetics ,Biotechnology ,Breast Cancer ,Estrogen ,Cancer ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Acyltransferases ,Adaptor Proteins ,Signal Transducing ,Animals ,Breast Neoplasms ,Carcinoma ,Ductal ,Breast ,Cell Division ,Cell Movement ,Cell Transformation ,Neoplastic ,Estrogens ,Female ,GTP-Binding Protein alpha Subunits ,Gq-G11 ,Gene Expression Regulation ,Neoplastic ,Hippo Signaling Pathway ,Humans ,Intracellular Signaling Peptides and Proteins ,Mice ,Mice ,Inbred BALB C ,Neoplasm Proteins ,Neoplasms ,Hormone-Dependent ,Phospholipase C beta ,Phosphoproteins ,Phosphorylation ,Protein Kinase C ,Protein Processing ,Post-Translational ,Protein Serine-Threonine Kinases ,RNA Interference ,Receptors ,Estrogen ,Receptors ,G-Protein-Coupled ,Serine-Threonine Kinase 3 ,Signal Transduction ,Transcription Factors ,Transcription ,Genetic ,Tumor Suppressor Proteins ,YAP-Signaling Proteins ,rho-Associated Kinases ,Medical and Health Sciences ,Immunology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
The G protein-coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis.
- Published
- 2015