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LIN28B Underlies the Pathogenesis of a Subclass of Ewing Sarcoma LIN28B Control of EWS-FLI1 Stability.
Keskin, Tugba; Bakaric, Arnaud; Waszyk, Patricia; Boulay, Gaylor; Torsello, Matteo; Cornaz-Buros, Sandrine; Chevalier, Nadja; Geiser, Thibaud; Martin, Patricia; Volorio, Angela; Iyer, Sowmya; Kulkarni, Anupriya; Letovanec, Igor; Cherix, Stéphane; Cote, Gregory M; Choy, Edwin; Digklia, Antonia; Montemurro, Michael; Chebib, Ivan; Nielsen, Petur G; Carcaboso, Angel M; Mora, Jaume; Renella, Raffaele; Suvà, Mario L; Fusco, Carlo; Provero, Paolo; Rivera, Miguel N; Riggi, Nicolò; Stamenkovic, Ivan.
Afiliación
  • Keskin T; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Bakaric A; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Waszyk P; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Boulay G; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Torsello M; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland; Department of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Cornaz-Buros S; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland; Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Chevalier N; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland; Department Woman-Mother-Child, Division of Pediatrics, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Geiser T; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Martin P; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Volorio A; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Iyer S; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Kulkarni A; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Letovanec I; Department of Pathology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Cherix S; Department of Orthopaedics and Traumatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Cote GM; Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Choy E; Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Digklia A; Department of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Montemurro M; Department of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Chebib I; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Nielsen PG; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Carcaboso AM; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, 08950 Barcelona, Spain.
  • Mora J; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, 08950 Barcelona, Spain.
  • Renella R; Department Woman-Mother-Child, Division of Pediatrics, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Suvà ML; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Fusco C; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Provero P; Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, 20132 Milan, Italy; Department of Molecular Biotechnology and Health Sciences, University of Turin, 10124 Turin, Italy.
  • Rivera MN; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Riggi N; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
  • Stamenkovic I; Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland. Electronic address: ivan.stamenkovic@chuv.ch.
Cell Rep ; 30(13): 4567-4583.e5, 2020 03 31.
Article en En | MEDLINE | ID: mdl-32234488
ABSTRACT
Ewing sarcoma (EwS) is associated with poor prognosis despite current multimodal therapy. Targeting of EWS-FLI1, the fusion protein responsible for its pathogenesis, and its principal downstream targets has not yet produced satisfactory therapeutic options, fueling the search for alternative approaches. Here, we show that the oncofetal RNA-binding protein LIN28B regulates the stability of EWS-FLI1 mRNA in ~10% of EwSs. LIN28B depletion in these tumors leads to a decrease in the expression of EWS-FLI1 and its direct transcriptional network, abrogating EwS cell self-renewal and tumorigenicity. Moreover, pharmacological inhibition of LIN28B mimics the effect of LIN28B depletion, suggesting that LIN28B sustains the emergence of a subset of EwS in which it also serves as an effective therapeutic target.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Sarcoma de Ewing / Proteínas de Fusión Oncogénica / Proteínas de Unión al ARN / Proteína EWS de Unión a ARN / Proteína Proto-Oncogénica c-fli-1 Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Sarcoma de Ewing / Proteínas de Fusión Oncogénica / Proteínas de Unión al ARN / Proteína EWS de Unión a ARN / Proteína Proto-Oncogénica c-fli-1 Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Suiza