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PMID: 16894141 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 33 ·2006-08-15 ·Pages 12405-10

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

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.

MeSH Terms
Adaptor Proteins, Signal Transducing/genetics,metabolism Animals Apoptosis/physiology Cell Cycle Proteins Cell Line, Tumor Cell Proliferation Cell Shape Cell Transformation, Neoplastic Chromosomes, Human, Pair 11 Drosophila Proteins/genetics,metabolism Epithelial Cells/cytology,metabolism Humans Mammary Glands, Human/cytology Mice Neoplasms/genetics,metabolism Nuclear Proteins/genetics,metabolism Oncogenes Phosphoproteins/genetics,metabolism Signal Transduction/physiology Trans-Activators/genetics,metabolism YAP-Signaling Proteins
Chemicals
Adaptor Proteins, Signal Transducing Cell Cycle Proteins Drosophila Proteins Nuclear Proteins Phosphoproteins Trans-Activators YAP-Signaling Proteins Yap1 protein, mouse Yki protein, Drosophila
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Overholtzer Michael
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Zhang Jianmin
Smolen Gromoslaw A
Muir Beth
Li Wenmei
Sgroi Dennis C
Deng Chu-Xia
Brugge Joan S
Haber Daniel A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0605579103
Published
2006-08-15
Epub
2006-00-07
Pages
12405-10
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1533802
Subset
IM
Grants
NCI NIH HHS · P01 CA95281 · United States
NCI NIH HHS · CA089393 · United States
NCI NIH HHS · P01 CA080111 · United States
NCI NIH HHS · P50 CA089393 · United States
NCI NIH HHS · T32CA09361 · United States
NCI NIH HHS · CA080111 · United States
NCI NIH HHS · F32 CA117737 · United States
NCI NIH HHS · T32 CA009361 · United States
External Links
PubMed source DOI: 10.1073/pnas.0605579103 PMC Full Text View journal details
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