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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

Authors

  • Overholtzer M
  • Zhang J
  • Smolen GA
  • Muir B
  • Li W
  • Sgroi DC
  • Deng CX
  • Brugge JS
  • Haber DA

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

August 15, 2006

Associated Grants

  • Agency: NCI NIH HHS, Id: CA080111
  • Agency: NCI NIH HHS, Id: CA089393
  • Agency: NCI NIH HHS, Id: F32 CA117737
  • Agency: NCI NIH HHS, Id: P01 CA95281
  • Agency: NCI NIH HHS, Id: T32CA09361

Mesh Terms

  • 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