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

Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12405-10. doi: 10.1073/pnas.0605579103. Epub 2006 Aug 7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis / physiology
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Shape
  • Cell Transformation, Neoplastic
  • Chromosomes, Human, Pair 11*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Humans
  • Mammary Glands, Human / cytology
  • Mice
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oncogenes*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Signal Transduction / physiology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Drosophila Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Trans-Activators
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • Yki protein, Drosophila