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Mutational and functional analysis reveals ADAMTS18 metalloproteinase as a novel driver in melanoma.
- Source :
-
Molecular cancer research : MCR [Mol Cancer Res] 2010 Nov; Vol. 8 (11), pp. 1513-25. Date of Electronic Publication: 2010 Oct 13. - Publication Year :
- 2010
-
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.<br /> (©2010 AACR.)
- Subjects :
- ADAMTS Proteins
Cell Adhesion genetics
Cell Growth Processes genetics
Cell Line, Tumor
Cell Movement genetics
DNA Mutational Analysis
Genes, Neoplasm
Humans
Melanoma pathology
Neoplasm Metastasis
ADAM Proteins genetics
ADAM Proteins metabolism
Melanoma enzymology
Melanoma genetics
Metalloproteases genetics
Metalloproteases metabolism
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3125
- Volume :
- 8
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Molecular cancer research : MCR
- Publication Type :
- Academic Journal
- Accession number :
- 21047771
- Full Text :
- https://doi.org/10.1158/1541-7786.MCR-10-0262