Comparative Oncogenomics Identifies NEDD9 as a Melanoma Metastasis Gene

Minjung Kim, Joseph D. Gans, Cristina Nogueira, Audrey Wang, Ji Hye Paik, Bin Feng, Cameron Brennan, William C. Hahn, Carlos Cordon-Cardo, Stephan N. Wagner, Thomas J. Flotte, Lyn M. Duncan, Scott R. Granter, Lynda Chin

Research output: Contribution to journalArticle

322 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1269-1281
Number of pages13
JournalCell
Volume125
Issue number7
DOIs
StatePublished - Jun 30 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    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. (2006). Comparative Oncogenomics Identifies NEDD9 as a Melanoma Metastasis Gene. Cell, 125(7), 1269-1281. https://doi.org/10.1016/j.cell.2006.06.008