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Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene.

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.

Pubmed ID: 16814714


  • Kim M
  • Gans JD
  • Nogueira C
  • Wang A
  • Paik JH
  • Feng B
  • Brennan C
  • Hahn WC
  • Cordon-Cardo C
  • Wagner SN
  • Flotte TJ
  • Duncan LM
  • Granter SR
  • Chin L



Publication Data

June 30, 2006

Associated Grants

  • Agency: NCI NIH HHS, Id: P50 CA093683
  • Agency: NCI NIH HHS, Id: P50 CA112962
  • Agency: NCI NIH HHS, Id: P50 CA93683
  • Agency: NCI NIH HHS, Id: R01 CA93947
  • Agency: NCI NIH HHS, Id: U01 CA105423
  • Agency: NCI NIH HHS, Id: U01 CA84313

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Base Sequence
  • DNA, Neoplasm
  • Female
  • Focal Adhesion Kinase 1
  • Gene Amplification
  • Gene Expression
  • Genomics
  • Humans
  • In Vitro Techniques
  • Melanocytes
  • Melanoma
  • Melanoma, Experimental
  • Mice
  • Mice, Knockout
  • Mice, SCID
  • Neoplasm Invasiveness
  • Oncogenes
  • Phosphoproteins
  • RNA Interference
  • Species Specificity