PMID- 25893606
OWN - NLM
STAT- MEDLINE
DCOM- 20150817
LR  - 20211203
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 125
IP  - 5
DP  - 2015 May
TI  - Estrogen regulates Hippo signaling via GPER in breast cancer.
PG  - 2123-35
LID - 79573 [pii]
LID - 10.1172/JCI79573 [doi]
AB  - 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.
FAU - Zhou, Xin
AU  - Zhou X
FAU - Wang, Shuyang
AU  - Wang S
FAU - Wang, Zhen
AU  - Wang Z
FAU - Feng, Xu
AU  - Feng X
FAU - Liu, Peng
AU  - Liu P
FAU - Lv, Xian-Bo
AU  - Lv XB
FAU - Li, Fulong
AU  - Li F
FAU - Yu, Fa-Xing
AU  - Yu FX
FAU - Sun, Yiping
AU  - Sun Y
FAU - Yuan, Haixin
AU  - Yuan H
FAU - Zhu, Hongguang
AU  - Zhu H
FAU - Xiong, Yue
AU  - Xiong Y
FAU - Lei, Qun-Ying
AU  - Lei QY
FAU - Guan, Kun-Liang
AU  - Guan KL
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150420
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Estrogens)
RN  - 0 (GPER1 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (TAFAZZIN protein, human)
RN  - EC 2.7.1.- (LATS1 protein, human)
RN  - EC 2.7.1.11 (STK4 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ROCK1 protein, human)
RN  - EC 2.7.11.1 (STK3 protein, human)
RN  - EC 2.7.11.1 (Serine-Threonine Kinase 3)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.1.4.11 (PLCB1 protein, human)
RN  - EC 3.1.4.11 (Phospholipase C beta)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
SB  - IM
MH  - Acyltransferases
MH  - Adaptor Proteins, Signal Transducing/physiology
MH  - Animals
MH  - Breast Neoplasms/genetics/metabolism/*physiopathology
MH  - Carcinoma, Ductal, Breast/genetics/metabolism/*physiopathology
MH  - Cell Division
MH  - Cell Movement
MH  - Cell Transformation, Neoplastic
MH  - Estrogens/pharmacology/*physiology
MH  - Female
MH  - GTP-Binding Protein alpha Subunits, Gq-G11/antagonists & 
      inhibitors/genetics/physiology
MH  - Gene Expression Regulation, Neoplastic
MH  - Hippo Signaling Pathway
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neoplasm Proteins/*physiology
MH  - Neoplasms, Hormone-Dependent/genetics/metabolism/*physiopathology
MH  - Phospholipase C beta/physiology
MH  - Phosphoproteins/physiology
MH  - Phosphorylation
MH  - Protein Kinase C/physiology
MH  - Protein Processing, Post-Translational
MH  - Protein Serine-Threonine Kinases/analysis/antagonists & 
      inhibitors/metabolism/*physiology
MH  - RNA Interference
MH  - Receptors, Estrogen/drug effects/*physiology
MH  - Receptors, G-Protein-Coupled/drug effects/*physiology
MH  - Serine-Threonine Kinase 3
MH  - Signal Transduction/*physiology
MH  - Transcription Factors/physiology
MH  - Transcription, Genetic
MH  - Tumor Suppressor Proteins/analysis/*physiology
MH  - YAP-Signaling Proteins
MH  - rho-Associated Kinases/physiology
PMC - PMC4463207
EDAT- 2015/04/22 06:00
MHDA- 2015/08/19 06:00
PMCR- 2015/08/01
CRDT- 2015/04/21 06:00
PHST- 2014/10/17 00:00 [received]
PHST- 2015/03/12 00:00 [accepted]
PHST- 2015/04/21 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2015/08/19 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - 79573 [pii]
AID - 10.1172/JCI79573 [doi]
PST - ppublish
SO  - J Clin Invest. 2015 May;125(5):2123-35. doi: 10.1172/JCI79573. Epub 2015 Apr 20.