title: Estrogen regulates Hippo signaling via GPER in breast cancer.
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.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Shuyang
authors.initials: S
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Lv
authors.forename: Fulong
authors.initials: F
authors.lastname: Li
authors.forename: Fa-Xing
authors.initials: FX
authors.lastname: Yu
authors.forename: Yiping
authors.initials: Y
authors.lastname: Sun
authors.forename: Haixin
authors.initials: H
authors.lastname: Yuan
authors.forename: Hongguang
authors.initials: H
authors.lastname: Zhu
authors.forename: Yue
authors.initials: Y
authors.lastname: Xiong
authors.forename: Qun-Ying
authors.initials: QY
authors.lastname: Lei
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002455:Cell Division; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D000090683:Hippo Signaling Pathway; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D054799:Phospholipase C beta / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology*; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000502:physiology*; D000091102:YAP-Signaling Proteins; D054460:rho-Associated Kinases / Q000502:physiology; D000099317:Hippo Kinases
chemical_list: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing; D004967:Estrogens; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D054799:Phospholipase C beta; D010750:Phosphoproteins; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D000090742:Serine-Threonine Kinase 3; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; D054460:rho-Associated Kinases; C109584:GPER1 protein, human; C088374:YAP1 protein, human; C108675:TAFAZZIN protein, human; C092745:LATS1 protein, human; C095566:STK4 protein, human; D000099317:Hippo Kinases; C515851:ROCK1 protein, human; C097835:STK3 protein, human; C518033:PLCB1 protein, human