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NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1.
Marques, Carolina; Unterkircher, Thomas; Kroon, Paula; Oldrini, Barbara; Izzo, Annalisa; Dramaretska, Yuliia; Ferrarese, Roberto; Kling, Eva; Schnell, Oliver; Nelander, Sven; Wagner, Erwin F; Bakiri, Latifa; Gargiulo, Gaetano; Carro, Maria Stella; Squatrito, Massimo.
Afiliación
  • Marques C; Seve Ballesteros Foundation Brain Tumor Group, Spanish National Cancer Research Centre, Madrid, Spain.
  • Unterkircher T; Department of Neurosurgery, Faculty of Medicine Freiburg, Freiburg, Germany.
  • Kroon P; Seve Ballesteros Foundation Brain Tumor Group, Spanish National Cancer Research Centre, Madrid, Spain.
  • Oldrini B; Seve Ballesteros Foundation Brain Tumor Group, Spanish National Cancer Research Centre, Madrid, Spain.
  • Izzo A; Department of Neurosurgery, Faculty of Medicine Freiburg, Freiburg, Germany.
  • Dramaretska Y; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
  • Ferrarese R; Department of Neurosurgery, Faculty of Medicine Freiburg, Freiburg, Germany.
  • Kling E; Department of Neurosurgery, Faculty of Medicine Freiburg, Freiburg, Germany.
  • Schnell O; Department of Neurosurgery, Faculty of Medicine Freiburg, Freiburg, Germany.
  • Nelander S; Dept of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Rudbecklaboratoriet, Uppsala, Sweden.
  • Wagner EF; Science for Life Laboratory, Uppsala University, Rudbecklaboratoriet, Uppsala, Sweden.
  • Bakiri L; Genes, Development, and Disease Group, Spanish National Cancer Research Centre, Madrid, Spain.
  • Gargiulo G; Laboratory Medicine Department, Medical University of Vienna, Vienna, Austria.
  • Carro MS; Dermatology Department, Medical University of Vienna, Vienna, Austria.
  • Squatrito M; Genes, Development, and Disease Group, Spanish National Cancer Research Centre, Madrid, Spain.
Elife ; 102021 08 17.
Article en En | MEDLINE | ID: mdl-34399888
The molecular basis underlying glioblastoma (GBM) heterogeneity and plasticity is not fully understood. Using transcriptomic data of human patient-derived brain tumor stem cell lines (BTSCs), classified based on GBM-intrinsic signatures, we identify the AP-1 transcription factor FOSL1 as a key regulator of the mesenchymal (MES) subtype. We provide a mechanistic basis to the role of the neurofibromatosis type 1 gene (NF1), a negative regulator of the RAS/MAPK pathway, in GBM mesenchymal transformation through the modulation of FOSL1 expression. Depletion of FOSL1 in NF1-mutant human BTSCs and Kras-mutant mouse neural stem cells results in loss of the mesenchymal gene signature and reduction in stem cell properties and in vivo tumorigenic potential. Our data demonstrate that FOSL1 controls GBM plasticity and aggressiveness in response to NF1 alterations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Neoplasias Encefálicas / Regulación Neoplásica de la Expresión Génica / Proteínas Proto-Oncogénicas c-fos / Glioblastoma / Neurofibromina 1 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Elife Año: 2021 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Neoplasias Encefálicas / Regulación Neoplásica de la Expresión Génica / Proteínas Proto-Oncogénicas c-fos / Glioblastoma / Neurofibromina 1 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Elife Año: 2021 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido