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Publication : Estrogen regulates Hippo signaling via GPER in breast cancer.

First Author  Zhou X Year  2015
Journal  J Clin Invest Volume  125
Issue  5 Pages  2123-35
PubMed ID  25893606 Mgi Jnum  J:222698
Mgi Id  MGI:5645403 Doi  10.1172/JCI79573
Citation  Zhou X, et al. (2015) Estrogen regulates Hippo signaling via GPER in breast cancer. J Clin Invest 125(5):2123-35
abstractText  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 Galphaq-11, PLCbeta/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.
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