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Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.
Aytes, Alvaro; Mitrofanova, Antonina; Lefebvre, Celine; Alvarez, Mariano J; Castillo-Martin, Mireia; Zheng, Tian; Eastham, James A; Gopalan, Anuradha; Pienta, Kenneth J; Shen, Michael M; Califano, Andrea; Abate-Shen, Cory.
Afiliación
  • Aytes A; Department of Urology, Columbia University Medical Center, New York, NY 10032.
  • Mitrofanova A; Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research, L'Hospitalet de Llobregat, Barcelona, Spain 08907.
  • Lefebvre C; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032.
  • Alvarez MJ; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032.
  • Castillo-Martin M; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032.
  • Zheng T; Department of Pathology, Icahn School of Medicine at Mount Sinai New York, NY 10029.
  • Eastham JA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032.
  • Gopalan A; Department of Statistics, Columbia University, New York, NY 10027.
  • Pienta KJ; Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
  • Shen MM; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
  • Califano A; The University of Michigan Ann Arbor, MI 48109, and the Brady Urological Institute at the Johns Hopkins School of Medicine, Baltimore, MD 21231.
  • Abate-Shen C; Department of Urology, Columbia University Medical Center, New York, NY 10032.
Cancer Cell ; 25(5): 638-651, 2014 May 12.
Article en En | MEDLINE | ID: mdl-24823640
To identify regulatory drivers of prostate cancer malignancy, we have assembled genome-wide regulatory networks (interactomes) for human and mouse prostate cancer from expression profiles of human tumors and of genetically engineered mouse models, respectively. Cross-species computational analysis of these interactomes has identified FOXM1 and CENPF as synergistic master regulators of prostate cancer malignancy. Experimental validation shows that FOXM1 and CENPF function synergistically to promote tumor growth by coordinated regulation of target gene expression and activation of key signaling pathways associated with prostate cancer malignancy. Furthermore, co-expression of FOXM1 and CENPF is a robust prognostic indicator of poor survival and metastasis. Thus, genome-wide cross-species interrogation of regulatory networks represents a valuable strategy to identify causal mechanisms of human cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Proteínas Cromosómicas no Histona / Factores de Transcripción Forkhead / Redes Reguladoras de Genes / Proteínas de Microfilamentos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Proteínas Cromosómicas no Histona / Factores de Transcripción Forkhead / Redes Reguladoras de Genes / Proteínas de Microfilamentos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos