MTSS1 is a metastasis driver in a subset of human melanomas

• Published in: Nature communications 2014-03, Vol.5 (1), p.3465, Article 3465
• Main Authors: Mertz, Kirsten D., Pathria, Gaurav, Wagner, Christine, Saarikangas, Juha, Sboner, Andrea, Romanov, Julia, Gschaider, Melanie, Lenz, Florian, Neumann, Friederike, Schreiner, Wolfgang, Nemethova, Maria, Glassmann, Alexander, Lappalainen, Pekka, Stingl, Georg, Small, J. Victor, Fink, Dieter, Chin, Lynda, Wagner, Stephan N.
• Format: Article
• Language: English
• Subjects: 631/67/1813/1634; 631/67/322; 631/67/68; 82/1; 82/29; 82/51; 82/80; Algorithms; Animals; Cancer; Cell adhesion & migration; Cell Line, Tumor; Disease; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genomes; Humanities and Social Sciences; Humans; Integrated approach; Laboratory animals; Medical prognosis; Medicine; Melanoma; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Metastasis; Mice, Nude; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; multidisciplinary; Neoplasm Metastasis; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Science; Science (multidisciplinary); Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms4465

In cancers with a highly altered genome, distinct genetic alterations drive subsets rather than the majority of individual tumours. Here we use a sequential search across human tumour samples for transcript outlier data points with associated gene copy number variations that correlate with patient’s survival to identify genes with pro-invasive functionality. Employing loss and gain of function approaches in vitro and in vivo , we show that one such gene, MTSS1 , promotes the ability of melanocytic cells to metastasize and engages actin dynamics via Rho-GTPases and cofilin in this process. Indeed, high MTSS1 expression defines a subgroup of primary melanomas with unfavourable prognosis. These data underscore the biological, clinical and potential therapeutic implications of molecular subsets within genetically complex cancers. Complex genomic alterations segregate melanoma into different molecular subsets, but for most subsets it is unclear whether they drive a distinct clinical behaviour. Here, the authors use gene-expression data from melanoma patients to search for outlier genes that correlate with survival and identify that MTSS1 is associated with metastasis.