期刊
MOLECULAR CANCER RESEARCH
卷 8, 期 11, 页码 1513-1525出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-10-0262
关键词
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资金
- National Human Genome Research Institute, NIH
- Ministerio de Ciencia e Innovacion-Spain
- Fundacion M. Botin
- European Union
- University of Texas
- M.D. Anderson Cancer Center
- Melanoma Informatics, Tissue Resource, and Pathology Core [P50 CA93459]
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. Mol Cancer Res; 8(11); 1513-25. (C) 2010 AACR.
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