Mutational and functional analysis reveals ADAMTS18 metalloproteinase as a novel driver in melanoma

Xiaomu Wei, Todd D. Prickett, Cristina G. Viloria, Alfredo Molinolo, Jimmy C. Lin, Isabel Cardenas-Navia, Pedro Cruz, Steven A. Rosenberg, Michael A. Davies, Jeffrey E. Gershenwald, Carlos López-Otín, Yardena Samuels

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


The disintegrin-metalloproteinases with thrombospondin domains (ADAMTS) genes have been suggested to function as tumor suppressors as several have been found to be epigenetically silenced in various cancers. We performed a mutational analysis of the ADAMTS gene family in human melanoma and identified a large fraction of melanomas to harbor somatic mutations. To evaluate the functional consequences of the most commonly mutated gene, ADAMTS18, six of its mutations were biologically examined. ADAMTS18 mutations had little effect on melanoma cell growth under standard conditions, but reduced cell dependence on growth factors. ADAMTS18 mutations also reduced adhesion to laminin and increased migration in vitro and metastasis in vivo. Melanoma cells expressing mutant ADAMTS18 had reduced cell migration after short hairpin RNA-mediated knockdown of ADAMTS18, suggesting that ADAMTS18 mutations promote growth, migration, and metastasis in melanoma.

Original languageEnglish (US)
Pages (from-to)1513-1525
Number of pages13
JournalMolecular Cancer Research
Issue number11
StatePublished - Nov 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research


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