Comparative Oncogenomics Identifies NEDD9 as a Melanoma Metastasis Gene

Cell. 2006 Jun 30;125(7):1269-81. doi: 10.1016/j.cell.2006.06.008.

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 types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA, Neoplasm
  • NEDD9 protein, human
  • Phosphoproteins
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Ptk2 protein, mouse