MTSS1 is a metastasis driver in a subset of human melanomas

Kirsten D. Mertz, Gaurav Pathria, Christine Wagner, Juha Saarikangas, Andrea Sboner, Julia Romanov, Melanie Gschaider, Florian Lenz, Friederike Neumann, Wolfgang Schreiner, Maria Nemethova, Alexander Glassmann, Pekka Lappalainen, Georg Stingl, J. Victor Small, Dieter Fink, Lynda Chin and Stephan N. Wagner ()
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Kirsten D. Mertz: Allergy and Infectious Diseases (DIAID), Medical University of Vienna
Gaurav Pathria: Allergy and Infectious Diseases (DIAID), Medical University of Vienna
Christine Wagner: Allergy and Infectious Diseases (DIAID), Medical University of Vienna
Juha Saarikangas: Institute of Biotechnology, University of Helsinki
Andrea Sboner: Institute for Computational Biomedicine, Weill Cornell Medical College
Julia Romanov: Allergy and Infectious Diseases (DIAID), Medical University of Vienna
Melanie Gschaider: Allergy and Infectious Diseases (DIAID), Medical University of Vienna
Florian Lenz: Section for Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna
Friederike Neumann: Section for Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna
Wolfgang Schreiner: Section for Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna
Maria Nemethova: Institute of Molecular Biotechnology, Austrian Academy of Sciences
Alexander Glassmann: Institute of Anatomy, University of Bonn
Pekka Lappalainen: Institute of Biotechnology, University of Helsinki
Georg Stingl: Allergy and Infectious Diseases (DIAID), Medical University of Vienna
J. Victor Small: Institute of Molecular Biotechnology, Austrian Academy of Sciences
Dieter Fink: Institute for Laboratory Animal Sciences, University for Veterinary Medicine
Lynda Chin: The University of Texas, M.D. Anderson Cancer Center
Stephan N. Wagner: Allergy and Infectious Diseases (DIAID), Medical University of Vienna

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms4465

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