Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon.
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.
Pubmed ID: 16894141 RIS Download
Adaptor Proteins, Signal Transducing | Animals | Apoptosis | Cell Line, Tumor | Cell Proliferation | Cell Shape | Cell Transformation, Neoplastic | Chromosomes, Human, Pair 11 | Drosophila Proteins | Epithelial Cells | Humans | Mammary Glands, Human | Mice | Neoplasms | Nuclear Proteins | Oncogenes | Phosphoproteins | Signal Transduction | Trans-Activators