Transforming Properties of YAP, a Candidate Oncogene on the Chromosome 11q22 Amplicon

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 33; pp. 12405 - 12410
• Main Authors: Overholtzer, Michael, Zhang, Jianmin, Smolen, Gromoslaw A., Muir, Beth, Li, Wenmei, Sgroi, Dennis C., Deng, Chu-Xia, Brugge, Joan S., Haber, Daniel A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15-08-2006; National Acad Sciences
• Subjects: 3T3 cells; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Apoptosis; Apoptosis - physiology; Biological Sciences; Cancer; Cell Cycle Proteins; Cell growth; Cell Line, Tumor; Cell lines; Cell Proliferation; Cell Shape; Cell Transformation, Neoplastic; Cells; Chromosomes; Chromosomes, Human, Pair 11; Drosophila; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - metabolism; Gene loci; Genes; Humans; Insects; Mammary Glands, Human - cytology; Mice; Neoplasms - genetics; Neoplasms - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncogenes; Phosphoproteins - genetics; Phosphoproteins - metabolism; Rodents; Signal Transduction - physiology; Trans-Activators - genetics; Trans-Activators - metabolism; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0605579103

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.