MTSS1 is a metastasis driver in a subset of human melanomas

被引：56

作者：

Mertz, Kirsten D. ^{[1
]}

Pathria, Gaurav ^{[1
]}

Wagner, Christine ^{[1
]}

Saarikangas, Juha ^{[2
]}

Sboner, Andrea ^{[3
]}

Romanov, Julia ^{[1
]}

Gschaider, Melanie ^{[1
]}

Lenz, Florian ^{[4
]}

Neumann, Friederike ^{[4
]}

Schreiner, Wolfgang ^{[4
]}

Nemethova, Maria ^{[5
]}

Glassmann, Alexander ^{[6
]}

Lappalainen, Pekka ^{[2
]}

Stingl, Georg ^{[1
]}

Small, J. Victor ^{[5
]}

Fink, Dieter ^{[7
]}

Chin, Lynda ^{[8
,9
]}

Wagner, Stephan N. ^{[1
,10
]}

机构：

[1] Med Univ Vienna, Dept Dermatol, Div Immunol Allergy & Infect Dis, A-1090 Vienna, Austria

[2] Univ Helsinki, Inst Biotechnol, SF-00100 Helsinki, Finland

[3] Weill Cornell Med Coll, Inst Computat Biomed, Dept Pathol & Lab Med, New York, NY 10021 USA

[4] Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, Sect Biosimulat & Bioinformat, A-1090 Vienna, Austria

[5] Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria

[6] Univ Bonn, Inst Anat, D-53113 Bonn, Germany

[7] Univ Vet Med, Dept Biomed Sci, Inst Lab Anim Sci, A-1210 Vienna, Austria

[8] Univ Texas Houston, MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[9] Univ Texas Houston, MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA

[10] Austrian Acad Sci, Ctr Mol Med CeMM, A-1090 Vienna, Austria

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

芬兰科学院; 奥地利科学基金会;

关键词：

COMPARATIVE GENOMIC HYBRIDIZATION; PROGRESSION MARKERS; ACTIN CYTOSKELETON; SOMATIC MUTATIONS; SUPPRESSOR GENE; CANCER; MIM; EXPRESSION; INHIBITION; COMPLEX;

D O I：

10.1038/ncomms4465

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 68 条

[1] An Integrated Approach to Uncover Drivers of Cancer [J].

Akavia, Uri David ;

Litvin, Oren ;

Kim, Jessica ;

Sanchez-Garcia, Felix ;

Kotliar, Dylan ;

Causton, Helen C. ;

Pochanard, Panisa ;

Mozes, Eyal ;

Garraway, Levi A. ;

Pe'er, Dana .

CELL, 2010, 143 (06) :1005-1017

[2] Correlated light and electron microscopy of the cytoskeleton [J].

Auinger, Sonja ;

Small, J. Victor .

INTRODUCTION TO ELECTRON MICROSCOPY FOR BIOLOGISTS, 2008, 88 :257-+

[3] Melanoma genome sequencing reveals frequent PREX2 mutations [J].

Berger, Michael F. ;

Hodis, Eran ;

Heffernan, Timothy P. ;

Deribe, Yonathan Lissanu ;

Lawrence, Michael S. ;

Protopopov, Alexei ;

Ivanova, Elena ;

Watson, Ian R. ;

Nickerson, Elizabeth ;

Ghosh, Papia ;

Zhang, Hailei ;

Zeid, Rhamy ;

Ren, Xiaojia ;

Cibulskis, Kristian ;

Sivachenko, Andrey Y. ;

Wagle, Nikhil ;

Sucker, Antje ;

Sougnez, Carrie ;

Onofrio, Robert ;

Ambrogio, Lauren ;

Auclair, Daniel ;

Fennell, Timothy ;

Carter, Scott L. ;

Drier, Yotam ;

Stojanov, Petar ;

Singer, Meredith A. ;

Voet, Douglas ;

Jing, Rui ;

Saksena, Gordon ;

Barretina, Jordi ;

Ramos, Alex H. ;

Pugh, Trevor J. ;

Stransky, Nicolas ;

Parkin, Melissa ;

Winckler, Wendy ;

Mahan, Scott ;

Ardlie, Kristin ;

Baldwin, Jennifer ;

Wargo, Jennifer ;

Schadendorf, Dirk ;

Meyerson, Matthew ;

Gabriel, Stacey B. ;

Golub, Todd R. ;

Wagner, Stephan N. ;

Lander, Eric S. ;

Getz, Gad ;

Chin, Lynda ;

Garraway, Levi A. .

NATURE, 2012, 485 (7399) :502-506

[4] ADF/Cofilin: a functional node in cell biology [J].

Bernstein, Barbara W. ;

Bamburg, James R. .

TRENDS IN CELL BIOLOGY, 2010, 20 (04) :187-195

[5] The landscape of somatic copy-number alteration across human cancers [J].

Beroukhim, Rameen ;

Mermel, Craig H. ;

Porter, Dale ;

Wei, Guo ;

Raychaudhuri, Soumya ;

Donovan, Jerry ;

Barretina, Jordi ;

Boehm, Jesse S. ;

Dobson, Jennifer ;

Urashima, Mitsuyoshi ;

Mc Henry, Kevin T. ;

Pinchback, Reid M. ;

Ligon, Azra H. ;

Cho, Yoon-Jae ;

Haery, Leila ;

Greulich, Heidi ;

Reich, Michael ;

Winckler, Wendy ;

Lawrence, Michael S. ;

Weir, Barbara A. ;

Tanaka, Kumiko E. ;

Chiang, Derek Y. ;

Bass, Adam J. ;

Loo, Alice ;

Hoffman, Carter ;

Prensner, John ;

Liefeld, Ted ;

Gao, Qing ;

Yecies, Derek ;

Signoretti, Sabina ;

Maher, Elizabeth ;

Kaye, Frederic J. ;

Sasaki, Hidefumi ;

Tepper, Joel E. ;

Fletcher, Jonathan A. ;

Tabernero, Josep ;

Baselga, Jose ;

Tsao, Ming-Sound ;

Demichelis, Francesca ;

Rubin, Mark A. ;

Janne, Pasi A. ;

Daly, Mark J. ;

Nucera, Carmelo ;

Levine, Ross L. ;

Ebert, Benjamin L. ;

Gabriel, Stacey ;

Rustgi, Anil K. ;

Antonescu, Cristina R. ;

Ladanyi, Marc ;

Letai, Anthony .

NATURE, 2010, 463 (7283) :899-905

[6] Involvement of Rac in actin cytoskeleton rearrangements induced by MIM-B [J].

Bompard, G ;

Sharp, SJ ;

Freiss, G ;

Machesky, LM .

JOURNAL OF CELL SCIENCE, 2005, 118 (22) :5393-5403

[7] Molecular mechanism of Ena/VASP-mediated actin-filament elongation [J].

Breitsprecher, Dennis ;

Kiesewetter, Antje K. ;

Linkner, Joern ;

Vinzenz, Marlene ;

Stradal, Theresia E. B. ;

Small, John Victor ;

Curth, Ute ;

Dickinson, Richard B. ;

Faix, Jan .

EMBO JOURNAL, 2011, 30 (03) :456-467

[8]

COX DR, 1972, J R STAT SOC B, V34, P187

[9] Distinct sets of genetic alterations in melanoma [J].

Curtin, JA ;

Fridlyand, J ;

Kageshita, T ;

Patel, HN ;

Busam, KJ ;

Kutzner, H ;

Cho, KH ;

Aiba, S ;

Bröcker, EB ;

LeBoit, PE ;

Pinkel, D ;

Bastian, BC .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (20) :2135-2147

[10] Mtss1 regulates epidermal growth factor signaling in head and neck squamous carcinoma cells [J].

Dawson, J. C. ;

Timpson, P. ;

Kalna, G. ;

Machesky, L. M. .

ONCOGENE, 2012, 31 (14) :1781-1793

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