PMID- 21666719
OWN - NLM
STAT- MEDLINE
DCOM- 20120229
LR  - 20211203
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 31
IP  - 2
DP  - 2012 Jan 12
TI  - Willin/FRMD6 expression activates the Hippo signaling pathway kinases in mammals 
      and antagonizes oncogenic YAP.
PG  - 238-50
LID - 10.1038/onc.2011.224 [doi]
AB  - The Salvador/Warts/Hippo (Hippo) signaling pathway defines a novel signaling 
      cascade regulating cell contact inhibition, organ size control, cell growth, 
      proliferation, apoptosis and cancer development in mammals. The Drosophila 
      melanogaster protein Expanded acts in the Hippo signaling pathway to control 
      organ size. Previously, willin/FRMD6 has been proposed as the human orthologue of 
      Expanded. Willin lacks C-terminal sequences that are present in Expanded and, to 
      date, little is known about the functional role of willin in mammalian cells. 
      When willin is expressed in D. melanogaster epithelial tissues, it has the same 
      subcellular localization as Expanded, but cannot rescue growth defects associated 
      with expanded deficiency. However, we show that ectopic willin expression causes 
      an increase in phosphorylation of the core Hippo signaling pathway components 
      MST1/2, LATS1 and YAP, an effect that can be antagonized by ezrin. In MCF10A 
      cells, loss of willin expression displays epithelial-to-mesenchymal transition 
      features and willin overexpression antagonizes YAP activity via the N-terminal 
      FERM domain of willin. Therefore, in mammalian cells willin influences Hippo 
      signaling activity by activating the core Hippo pathway kinase cassette.
FAU - Angus, L
AU  - Angus L
AD  - School of Biology, University of St Andrews, St Andrews, UK.
FAU - Moleirinho, S
AU  - Moleirinho S
FAU - Herron, L
AU  - Herron L
FAU - Sinha, A
AU  - Sinha A
FAU - Zhang, X
AU  - Zhang X
FAU - Niestrata, M
AU  - Niestrata M
FAU - Dholakia, K
AU  - Dholakia K
FAU - Prystowsky, M B
AU  - Prystowsky MB
FAU - Harvey, K F
AU  - Harvey KF
FAU - Reynolds, P A
AU  - Reynolds PA
FAU - Gunn-Moore, F J
AU  - Gunn-Moore FJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110613
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (FRMD6 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Yki protein, Drosophila)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (hpo protein, Drosophila)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Line
MH  - Cytoskeletal Proteins/*metabolism
MH  - Drosophila Proteins/*antagonists & inhibitors/*metabolism
MH  - Drosophila melanogaster
MH  - Epithelial-Mesenchymal Transition
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Membrane Proteins/*metabolism
MH  - Nuclear Proteins/*antagonists & inhibitors
MH  - *Oncogenes
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - *Signal Transduction
MH  - Subcellular Fractions/metabolism
MH  - Trans-Activators/*antagonists & inhibitors
MH  - YAP-Signaling Proteins
EDAT- 2011/06/15 06:00
MHDA- 2012/03/01 06:00
CRDT- 2011/06/14 06:00
PHST- 2011/06/14 06:00 [entrez]
PHST- 2011/06/15 06:00 [pubmed]
PHST- 2012/03/01 06:00 [medline]
AID - onc2011224 [pii]
AID - 10.1038/onc.2011.224 [doi]
PST - ppublish
SO  - Oncogene. 2012 Jan 12;31(2):238-50. doi: 10.1038/onc.2011.224. Epub 2011 Jun 13.