Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene Journal Article

  


Authors: Kim, M.; Gans, J. D.; Nogueira, C.; Wang, A.; Paik, J. H.; Feng, B.; Brennan, C.; Hahn, W. C.; Cordon-Cardo, C.; Wagner, S. N.; Flotte, T. J.; Duncan, L. M.; Granter, S. R.; Chin, L.
Article Title: Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene
Abstract: Genomes of human cancer cells are characterized by numerous chromosomal aberrations of uncertain pathogenetic significance. Here, in an inducible mouse model of melanoma, we characterized metastatic variants with an acquired focal chromosomal amplification that corresponds to a much larger amplification in human metastatic melanomas. Further analyses identified Nedd9, an adaptor protein related to p130CAS, as the only gene within the minimal common region that exhibited amplification-associated overexpression. A series of functional, biochemical, and clinical studies established NEDD9 as a bona fide melanoma metastasis gene. NEDD9 enhanced invasion in vitro and metastasis in vivo of both normal and transformed melanocytes, functionally interacted with focal adhesion kinase and modulated focal contact formation, and exhibited frequent robust overexpression in human metastatic melanoma relative to primary melanoma. Thus, comparative oncogenomics has enabled the identification and facilitated the validation of a highly relevant cancer gene governing metastatic potential in human melanoma. © 2006 Elsevier Inc. All rights reserved.
Keywords: unclassified drug; human cell; nonhuman; comparative study; mouse; animals; mice; mice, knockout; gene overexpression; melanoma; metastasis; gene amplification; gene expression; melanocyte; melanocytes; animal experiment; rna interference; in vivo study; in vitro study; mice, scid; validation study; oncogenes; cancer invasion; cancer genetics; chromosome aberration; oncogene; species specificity; gene identification; dna, neoplasm; melanoma cell; melanoma, experimental; adaptor proteins, signal transducing; phosphoproteins; genomics; base sequence; genome; neoplasm invasiveness; malignant transformation; chromosome analysis; focal adhesion kinase; focal adhesion kinase 1; adaptor protein; nedd9 protein
Journal Title: Cell
Volume: 125
Issue: 7
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2006-06-30
Start Page: 1269
End Page: 1281
Language: English
DOI: 10.1016/j.cell.2006.06.008
PUBMED: 16814714
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-33745288277&partnerID=40&md5=daedca62488e06aac8dba4435f5bfedd
Notes: --- - "Cited By (since 1996): 150" - "Export Date: 4 June 2012" - "CODEN: CELLB" - "Source: Scopus"
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  1. Cameron Brennan
    226 Brennan
  2. Carlos Cordon-Cardo
    612 Cordon-Cardo
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