PMID- 19935651
OWN - NLM
STAT- MEDLINE
DCOM- 20091221
LR  - 20220129
IS  - 1476-4679 (Electronic)
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 11
IP  - 12
DP  - 2009 Dec
TI  - YAP-dependent induction of amphiregulin identifies a non-cell-autonomous 
      component of the Hippo pathway.
PG  - 1444-50
LID - 10.1038/ncb1993 [doi]
AB  - The Hippo signalling pathway regulates cellular proliferation and survival, thus 
      has profound effects on normal cell fate and tumorigenesis. The pivotal effector 
      of this pathway is YAP (yes-associated protein), a transcriptional co-activator 
      amplified in mouse and human cancers, where it promotes epithelial to mesenchymal 
      transition (EMT) and malignant transformation. So far, studies of YAP target 
      genes have focused on cell-autonomous mediators; here we show that YAP-expressing 
      MCF10A breast epithelial cells enhance the proliferation of neighbouring 
      untransfected cells, implicating a non-cell-autonomous mechanism. We identify the 
      gene for the epidermal growth factor receptor (EGFR) ligand amphiregulin (AREG) 
      as a transcriptional target of YAP, whose induction contributes to YAP-mediated 
      cell proliferation and migration, but not EMT. Knockdown of AREG or addition of 
      an EGFR kinase inhibitor abrogates the proliferative effects of YAP expression. 
      Suppression of the negative YAP regulators LATS1 and 2 (large tumour suppressor 1 
      and 2) is sufficient to induce AREG expression, consistent with physiological 
      regulation of AREG by the Hippo pathway. Genetic interaction between the 
      Drosophila YAP orthologue Yorkie and Egfr signalling components supports the link 
      between these two highly conserved signalling pathways. Thus, YAP-dependent 
      secretion of AREG indicates that activation of EGFR signalling is an important 
      non-cell-autonomous effector of the Hippo pathway, which has implications for the 
      regulation of both physiological and malignant cell proliferation.
FAU - Zhang, Jianmin
AU  - Zhang J
AD  - Massachusetts General Hospital Cancer Center, Harvard Medical School, 
      Charlestown, MA 02129, USA.
FAU - Ji, Jun-Yuan
AU  - Ji JY
FAU - Yu, Min
AU  - Yu M
FAU - Overholtzer, Michael
AU  - Overholtzer M
FAU - Smolen, Gromoslaw A
AU  - Smolen GA
FAU - Wang, Rebecca
AU  - Wang R
FAU - Brugge, Joan S
AU  - Brugge JS
FAU - Dyson, Nicholas J
AU  - Dyson NJ
FAU - Haber, Daniel A
AU  - Haber DA
LA  - eng
GR  - GM81607/GM/NIGMS NIH HHS/United States
GR  - P01 CA080111/CA/NCI NIH HHS/United States
GR  - P50 CA089393/CA/NCI NIH HHS/United States
GR  - R01 GM081607-02/GM/NIGMS NIH HHS/United States
GR  - GM053203/GM/NIGMS NIH HHS/United States
GR  - T32 CA09361-27/CA/NCI NIH HHS/United States
GR  - F32 CA009361/CA/NCI NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - CA089393/CA/NCI NIH HHS/United States
GR  - R01 GM053203/GM/NIGMS NIH HHS/United States
GR  - R01 95281/PHS HHS/United States
GR  - CA080111/CA/NCI NIH HHS/United States
GR  - F32 CA117737/CA/NCI NIH HHS/United States
GR  - R01 GM081607/GM/NIGMS NIH HHS/United States
GR  - T32 CA09361/CA/NCI NIH HHS/United States
GR  - T32 CA009361/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 - 20091122
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Areg protein, mouse)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Drosophila 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 (Nuclear Proteins)
RN  - 0 (Receptors, Invertebrate Peptide)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YY1AP1 protein, human)
RN  - 0 (Yki protein, Drosophila)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (Egfr protein, Drosophila)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (hpo protein, Drosophila)
SB  - IM
MH  - Amphiregulin
MH  - Animals
MH  - Cell Cycle Proteins
MH  - Cell Line, Tumor
MH  - Drosophila Proteins/genetics/*metabolism
MH  - Drosophila melanogaster/genetics/*metabolism
MH  - EGF Family of Proteins
MH  - ErbB Receptors/genetics/metabolism
MH  - Female
MH  - Glycoproteins/genetics/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Receptors, Invertebrate Peptide/metabolism
MH  - *Signal Transduction
MH  - Trans-Activators/genetics/*metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - YAP-Signaling Proteins
PMC - PMC2819909
MID - NIHMS172001
EDAT- 2009/11/26 06:00
MHDA- 2009/12/22 06:00
PMCR- 2010/06/01
CRDT- 2009/11/26 06:00
PHST- 2009/07/14 00:00 [received]
PHST- 2009/08/12 00:00 [accepted]
PHST- 2009/11/26 06:00 [entrez]
PHST- 2009/11/26 06:00 [pubmed]
PHST- 2009/12/22 06:00 [medline]
PHST- 2010/06/01 00:00 [pmc-release]
AID - ncb1993 [pii]
AID - 10.1038/ncb1993 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2009 Dec;11(12):1444-50. doi: 10.1038/ncb1993. Epub 2009 Nov 22.