Nf1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the ap-1 transcription factor fosl1
Marques C, Unterkircher T, Kroon P, Oldrini B, Izzo A, Dramaretska Y, Ferrarese R, Kling E, Schnell O, Nelander S, Wagner EF, Bakiri L, Gargiulo G, Carro MS, Squatrito M (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 10
Article Number: e64846
DOI: 10.7554/ELIFE.64846
Abstract
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.
Authors with CRIS profile
Involved external institutions
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
Spain (ES)
Universitätsklinikum Freiburg
Germany (DE)
Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Germany (DE)
Uppsala University
Sweden (SE)
Spain (ES)
Universitätsklinikum Freiburg
Germany (DE)
Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Germany (DE)
Uppsala University
Sweden (SE)
How to cite
APA:
Marques, C., Unterkircher, T., Kroon, P., Oldrini, B., Izzo, A., Dramaretska, Y.,... Squatrito, M. (2021). Nf1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the ap-1 transcription factor fosl1. eLife, 10. https://doi.org/10.7554/ELIFE.64846
MLA:
Marques, Carolina, et al. "Nf1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the ap-1 transcription factor fosl1." eLife 10 (2021).
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