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Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12405-10. Epub 2006 Aug 7.

Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon.

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  • 1Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Abstract

In a screen for gene copy-number changes in mouse mammary tumors, we identified a tumor with a small 350-kb amplicon from a region that is syntenic to a much larger locus amplified in human cancers at chromosome 11q22. The mouse amplicon contains only one known gene, Yap, encoding the mammalian ortholog of Drosophila Yorkie (Yki), a downstream effector of the Hippo(Hpo)-Salvador(Sav)-Warts(Wts) signaling cascade, recently identified in flies as a critical regulator of cellular proliferation and apoptosis. In nontransformed mammary epithelial cells, overexpression of human YAP induces epithelial-to-mesenchymal transition, suppression of apoptosis, growth factor-independent proliferation, and anchorage-independent growth in soft agar. Together, these observations point to a potential oncogenic role for YAP in 11q22-amplified human cancers, and they suggest that this highly conserved signaling pathway identified in Drosophila regulates both cellular proliferation and apoptosis in mammalian epithelial cells.

PMID:
16894141
[PubMed - indexed for MEDLINE]
PMCID:
PMC1533802
Free PMC Article
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