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Inactivation of Capicua drives cancer metastasis.
Okimoto, Ross A; Breitenbuecher, Frank; Olivas, Victor R; Wu, Wei; Gini, Beatrice; Hofree, Matan; Asthana, Saurabh; Hrustanovic, Gorjan; Flanagan, Jennifer; Tulpule, Asmin; Blakely, Collin M; Haringsma, Henry J; Simmons, Andrew D; Gowen, Kyle; Suh, James; Miller, Vincent A; Ali, Siraj; Schuler, Martin; Bivona, Trever G.
Afiliação
  • Okimoto RA; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Breitenbuecher F; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Olivas VR; Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany.
  • Wu W; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Gini B; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Hofree M; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Asthana S; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Hrustanovic G; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Flanagan J; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Tulpule A; Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
  • Blakely CM; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Haringsma HJ; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Simmons AD; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Gowen K; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Suh J; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Miller VA; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Ali S; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Schuler M; Clovis Oncology Inc., San Francisco, California, USA.
  • Bivona TG; Clovis Oncology Inc., San Francisco, California, USA.
Nat Genet ; 49(1): 87-96, 2017 01.
Article em En | MEDLINE | ID: mdl-27869830
ABSTRACT
Metastasis is the leading cause of death in people with lung cancer, yet the molecular effectors underlying tumor dissemination remain poorly defined. Through the development of an in vivo spontaneous lung cancer metastasis model, we show that the developmentally regulated transcriptional repressor Capicua (CIC) suppresses invasion and metastasis. Inactivation of CIC relieves repression of its effector ETV4, driving ETV4-mediated upregulation of MMP24, which is necessary and sufficient for metastasis. Loss of CIC, or an increase in levels of its effectors ETV4 and MMP24, is a biomarker of tumor progression and worse outcomes in people with lung and/or gastric cancer. Our findings reveal CIC as a conserved metastasis suppressor, highlighting new anti-metastatic strategies that could potentially improve patient outcomes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Proteínas Proto-Oncogênicas / Proteínas E1A de Adenovirus / Carcinoma Pulmonar de Células não Pequenas / Metaloproteinases da Matriz Associadas à Membrana / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Proteínas Proto-Oncogênicas / Proteínas E1A de Adenovirus / Carcinoma Pulmonar de Células não Pequenas / Metaloproteinases da Matriz Associadas à Membrana / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article