期刊
ONCOGENE
卷 32, 期 14, 页码 1821-1830出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2012.196
关键词
KIBRA; Hippo pathway; Merlin; Willin; breast cancer; claudin-low
资金
- Scottish University Life Science Alliance
- Breakthrough Breast Cancer
- National Health and Medical Research Council of Australia
- New South Wales Cancer Council
- Cancer Institute New South Wales
- Banque Nationale de Paris-Paribas Australia
- Banque Nationale de Paris-Paribas New Zealand
- RT Hall Trust
- Australian Cancer Research Foundation
- National Breast Cancer Foundation
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 upstream regulation of this pathway has been less well defined than the core kinase cassette. KIBRA has been shown to function as an upstream member of the Hippo pathway by influencing the phosphorylation of LATS and YAP, but functional consequences of these biochemical changes have not been previously addressed. We show that in MCF10A cells, loss of KIBRA expression displays epithelial-to-mesenchymal transition (EMT) features, which are concomitant with decreased LATS and YAP phosphorylation, but not MST1/2. In addition, ectopic KIBRA expression antagonizes YAP via the serine 127 phosphorylation site and we show that KIBRA, Willin and Merlin differentially regulate genes controlled by YAP. Finally, reduced KIBRA expression in primary breast cancer specimens correlates with the recently described claudin-low subtype, an aggressive sub-group with EMT features and a poor prognosis. Oncogene (2013) 32, 1821-1830; doi: 10.1038/onc.2012.196; published online 21 May 2012
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