Journal
ONCOGENE
Volume 31, Issue 2, Pages 238-250Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.224
Keywords
Willin/FRMD6; Expanded; Hippo pathway; ezrin; merlin
Funding
- BBSRC
- EPSRC
- Scottish University Life Science Alliance
- International Human Frontier Science Program Organization
- National Health and Medical Research Council of Australia
- Melbourne International Research Scholarship
- Fee Remission Scholarship
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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. Oncogene (2012) 31, 238-250; doi:10.1038/onc.2011.224; published online 13 June 2011
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