Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Wei X

PROVIDER: S-EPMC3058631 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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

Wei Xiaomu X Prickett Todd D TD Viloria Cristina G CG Molinolo Alfredo A Lin Jimmy C JC Cardenas-Navia Isabel I Cruz Pedro P Rosenberg Steven A SA Davies Michael A MA Gershenwald Jeffrey E JE López-Otín Carlos C Samuels Yardena Y

Molecular cancer research : MCR 20101013 11

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. ADAMT ...[more]

PMID: 21047771

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Dataset Information

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

Publications

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

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