NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1
| Item Type: | Preprint |
|---|
| Title: | NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1 |
|---|
| Creators Name: | Marques, C. and Unterkircher, T. and Kroon, P. and Izzo, A. and Gargiulo, G. and Kling, E. and Schnell, O. and Nelander, S. and Wagner, E.F. and Bakiri, L. and Carro, M.S. and Squatrito, M. |
|---|
| Abstract: | Summary: The molecular basis underlying Glioblastoma (GBM) heterogeneity and plasticity are not fully understood. Using transcriptomic data of patient-derived brain tumor stem cell lines (BTSCs), classified based on GBM-intrinsic signatures, we identify the AP-1 transcription factor FOSL1 as a master 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, 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. |
|---|
| Keywords: | GBM, Mesenchymal, NF1, FOSL1, FRA-1, Master Regulator |
|---|
| Source: | bioRxiv |
|---|
| Publisher: | Cold Spring Harbor Laboratory Press |
|---|
| Article Number: | 834531 |
|---|
| Date: | 7 November 2019 |
|---|
| Official Publication: | https://doi.org/10.1101/834531 |
|---|
| Related to: | |
|---|
Repository Staff Only: item control page
Downloads per month over past year
|
![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Download Statistics
Download Statistics
