title: MTSS1 is a metastasis driver in a subset of human melanomas.
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.
authors.affiliation: 1] Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria [2] [3].
authors.forename: Kirsten D
authors.initials: KD
authors.lastname: Mertz
authors.affiliation: 1] Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria [2].
authors.forename: Gaurav
authors.initials: G
authors.lastname: Pathria
authors.affiliation: 1] Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria [2].
authors.forename: Christine
authors.initials: C
authors.lastname: Wagner
authors.affiliation: 1] Institute of Biotechnology, University of Helsinki, 00100 Helsinki, Finland [2].
authors.forename: Juha
authors.initials: J
authors.lastname: Saarikangas
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York 10021, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sboner
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Romanov
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Melanie
authors.initials: M
authors.lastname: Gschaider
authors.affiliation: Section for Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Lenz
authors.affiliation: Section for Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Friederike
authors.initials: F
authors.lastname: Neumann
authors.affiliation: Section for Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schreiner
authors.affiliation: Institute of Molecular Biotechnology, Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Nemethova
authors.affiliation: 1] Institute of Anatomy, University of Bonn, 53113 Bonn, Germany [2].
authors.forename: Alexander
authors.initials: A
authors.lastname: Glassmann
authors.affiliation: Institute of Biotechnology, University of Helsinki, 00100 Helsinki, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Lappalainen
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Stingl
authors.affiliation: Institute of Molecular Biotechnology, Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: J Victor
authors.initials: JV
authors.lastname: Small
authors.affiliation: Institute for Laboratory Animal Sciences, Department of Biomedical Sciences, University for Veterinary Medicine, 1210 Vienna, Austria.
authors.forename: Dieter
authors.initials: D
authors.lastname: Fink
authors.affiliation: Department of Genomic Medicine and Institute for Applied Cancer Science, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.affiliation: 1] Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria [2] Center for Molecular Medicine (CeMM), Austrian Academy of Sciences, 1090 Vienna, Austria.
authors.forename: Stephan N
authors.initials: SN
authors.lastname: Wagner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C486778:MTSS1 protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins