Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene. Academic Article uri icon

Overview

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.

publication date

  • June 30, 2006

Research

keywords

  • Adaptor Proteins, Signal Transducing
  • Melanoma
  • Oncogenes
  • Phosphoproteins

Identity

Scopus Document Identifier

  • 33745288277

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2006.06.008

PubMed ID

  • 16814714

Additional Document Info

volume

  • 125

issue

  • 7