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KRAS and YAP1 converge to regulate EMT and tumor survival.
Shao, Diane D; Xue, Wen; Krall, Elsa B; Bhutkar, Arjun; Piccioni, Federica; Wang, Xiaoxing; Schinzel, Anna C; Sood, Sabina; Rosenbluh, Joseph; Kim, Jong W; Zwang, Yaara; Roberts, Thomas M; Root, David E; Jacks, Tyler; Hahn, William C.
Afiliação
  • Shao DD; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Xue W; Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA.
  • Krall EB; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Bhutkar A; Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA.
  • Piccioni F; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Wang X; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Schinzel AC; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Sood S; Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA.
  • Rosenbluh J; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Kim JW; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Zwang Y; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Roberts TM; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA.
  • Root DE; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Jacks T; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic addr
  • Hahn WC; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: william_hahn@dfci.harvard.edu.
Cell ; 158(1): 171-84, 2014 Jul 03.
Article em En | MEDLINE | ID: mdl-24954536
Cancer cells that express oncogenic alleles of RAS typically require sustained expression of the mutant allele for survival, but the molecular basis of this oncogene dependency remains incompletely understood. To identify genes that can functionally substitute for oncogenic RAS, we systematically expressed 15,294 open reading frames in a human KRAS-dependent colon cancer cell line engineered to express an inducible KRAS-specific shRNA. We found 147 genes that promoted survival upon KRAS suppression. In particular, the transcriptional coactivator YAP1 rescued cell viability in KRAS-dependent cells upon suppression of KRAS and was required for KRAS-induced cell transformation. Acquired resistance to Kras suppression in a Kras-driven murine lung cancer model also involved increased YAP1 signaling. KRAS and YAP1 converge on the transcription factor FOS and activate a transcriptional program involved in regulating the epithelial-mesenchymal transition (EMT). Together, these findings implicate transcriptional regulation of EMT by YAP1 as a significant component of oncogenic RAS signaling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfoproteínas / Sobrevivência Celular / Proteínas Proto-Oncogênicas / Neoplasias do Colo / Proteínas ras / Resistencia a Medicamentos Antineoplásicos / Proteínas Adaptadoras de Transdução de Sinal / Transição Epitelial-Mesenquimal / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfoproteínas / Sobrevivência Celular / Proteínas Proto-Oncogênicas / Neoplasias do Colo / Proteínas ras / Resistencia a Medicamentos Antineoplásicos / Proteínas Adaptadoras de Transdução de Sinal / Transição Epitelial-Mesenquimal / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article