PMID- 22825057
OWN - NLM
STAT- MEDLINE
DCOM- 20130201
LR  - 20211203
IS  - 1551-4005 (Electronic)
IS  - 1538-4101 (Print)
IS  - 1551-4005 (Linking)
VI  - 11
IP  - 15
DP  - 2012 Aug 1
TI  - TAZ induces growth factor-independent proliferation through activation of EGFR 
      ligand amphiregulin.
PG  - 2922-30
LID - 10.4161/cc.21386 [doi]
AB  - The Hippo signaling pathway regulates cellular proliferation and survival, thus 
      exerting profound effects on normal cell fate and tumorigenesis. We previously 
      showed that the pivotal effector of this pathway, YAP, is amplified in tumors and 
      promotes epithelial-to-mesenchymal transition (EMT) and malignant transformation. 
      Here, we report that overexpression of TAZ, a paralog of YAP, in human mammary 
      epithelial cells promotes EMT and, in particular, some invasive structures in 3D 
      cultures. TAZ also leads to cell migration and anchorage-independent growth in 
      soft agar. Furthermore, we identified amphiregulin (AREG), an epidermal growth 
      factor receptor (EGFR) ligand, as a target of TAZ. We show that AREG functions in 
      a non-cell-autonomous manner to mediate EGF-independent growth and malignant 
      behavior of mammary epithelial cells. In addition, ablation of TEAD binding 
      completely abolishes the TAZ-induced phenotype. Last, analysis of breast cancer 
      patient samples reveals a positive correlation between TAZ and AREG in vivo. In 
      summary, TAZ-dependent secretion of AREG indicates that activation of the EGFR 
      signaling is an important non-cell-autonomous effector of the Hippo pathway, and 
      TAZ as well as its targets may play significant roles in breast tumorigenesis and 
      metastasis.
FAU - Yang, Nuo
AU  - Yang N
AD  - Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
FAU - Morrison, Carl D
AU  - Morrison CD
FAU - Liu, Peijun
AU  - Liu P
FAU - Miecznikowski, Jeff
AU  - Miecznikowski J
FAU - Bshara, Wiam
AU  - Bshara W
FAU - Han, Suxia
AU  - Han S
FAU - Zhu, Qing
AU  - Zhu Q
FAU - Omilian, Angela R
AU  - Omilian AR
FAU - Li, Xu
AU  - Li X
FAU - Zhang, Jianmin
AU  - Zhang J
LA  - eng
GR  - P30 CA016056/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120801
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Transcriptional Coactivator with PDZ-Binding Motif Proteins)
RN  - 0 (WWTR1 protein, human)
RN  - 0 (YY1AP1 protein, human)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Amphiregulin
MH  - Breast Neoplasms/*metabolism
MH  - Cell Cycle Proteins
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - *Cell Transformation, Neoplastic
MH  - EGF Family of Proteins
MH  - Epithelial Cells/metabolism
MH  - Epithelial-Mesenchymal Transition
MH  - ErbB Receptors/*metabolism
MH  - Female
MH  - Glycoproteins/genetics/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Ligands
MH  - Mammary Glands, Human/*metabolism/pathology
MH  - Neoplasm Metastasis
MH  - Nuclear Proteins/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering
MH  - Signal Transduction
MH  - Trans-Activators
MH  - Transcription Factors
MH  - Transcriptional Coactivator with PDZ-Binding Motif Proteins
PMC - PMC3419062
EDAT- 2012/07/25 06:00
MHDA- 2013/02/05 06:00
PMCR- 2013/08/01
CRDT- 2012/07/25 06:00
PHST- 2012/07/25 06:00 [entrez]
PHST- 2012/07/25 06:00 [pubmed]
PHST- 2013/02/05 06:00 [medline]
PHST- 2013/08/01 00:00 [pmc-release]
AID - 21386 [pii]
AID - 2012CC4266 [pii]
AID - 10.4161/cc.21386 [doi]
PST - ppublish
SO  - Cell Cycle. 2012 Aug 1;11(15):2922-30. doi: 10.4161/cc.21386. Epub 2012 Aug 1.