NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1

zu Verbundenen Objekten

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

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
eLife. - 10 (2021) , e64846, ISSN: 2050-084X

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2021
Urheber
Marques, Carolina
Unterkircher, Thomas
Kroon, Paula
Oldrini, Barbara
Izzo, Annalisa
Dramaretska, Yuliia
Ferrarese, Roberto
Kling, Eva
Schnell, Oliver
Nelander, Sven
Wagner, Erwin Friedrich
Bakiri, Latifa
Gargiulo, Gaetano
Carro, Maria Stella
Squatrito, Massimo

DOI
10.7554/eLife.64846
URN
urn:nbn:de:bsz:25-freidok-2216455
Rechteinformation
Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:39 MESZ

Datenpartner

Dieses Objekt wird bereitgestellt von:
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Original beim Datenpartner anzeigen

Beteiligte

Entstanden

  • 2021

Ähnliche Objekte (12)

Neuroprotektive Funktion des ciliary neurotrophic factor : Untersuchungen an CNTF-defizienten Mäusen nach Läsion der septohippokampalen Projektion

Hochschulschrift

Neuroprotektive Funktion des ciliary neurotrophic factor : Untersuchungen an CNTF-defizienten Mäusen nach Läsion der septohippokampalen Projektion

Neuroprotektive Funktion des ciliary neurotrophic factor : Untersuchungen an CNTF-defizienten Mäusen nach Läsion der septohippokampalen Projektion

Hochschulschrift

Neuroprotektive Funktion des ciliary neurotrophic factor : Untersuchungen an CNTF-defizienten Mäusen nach Läsion der septohippokampalen Projektion

Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419)

Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419)

Distinct glioblastoma subgroups expression altered by metabolic microenvironment

Distinct glioblastoma subgroups expression altered by metabolic microenvironment

Immune escape mechanisms in neurooncology : : comprehensive analysis of PD-L1 expression and pathway regulation in de-novo and recurrent glioblastoma multiforme

Immune escape mechanisms in neurooncology : : comprehensive analysis of PD-L1 expression and pathway regulation in de-novo and recurrent glioblastoma multiforme

Increased apoptotic sensitivity of glioblastoma enables therapeutic targeting by BH3-mimetics

Increased apoptotic sensitivity of glioblastoma enables therapeutic targeting by BH3-mimetics

Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial

Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial

A vaccine targeting mutant IDH1 in newly diagnosed glioma

A vaccine targeting mutant IDH1 in newly diagnosed glioma

Proposed definition of competencies for surgical neuro-oncology training

Proposed definition of competencies for surgical neuro-oncology training

Prognostic validation of a new classification system for extent of resection in glioblastoma: a report of the RANO resect group

Prognostic validation of a new classification system for extent of resection in glioblastoma: a report of the RANO resect group

Surgical treatment of glioblastoma: State-of-the-art and future trends

Surgical treatment of glioblastoma: State-of-the-art and future trends

Surgical management and outcome of newly diagnosed glioblastoma without contrast enhancement (low-grade appearance): a report of the RANO resect group

Surgical management and outcome of newly diagnosed glioblastoma without contrast enhancement (low-grade appearance): a report of the RANO resect group

Verbundene Objekte