The HIF1α/JMY pathway promotes glioblastoma stem-like cell invasiveness after irradiation.
Cell Line, Tumor
Cell Movement
/ genetics
Cell Nucleus
/ metabolism
Cytoplasm
/ metabolism
Glioblastoma
/ metabolism
Glioma
/ metabolism
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
Nuclear Proteins
/ genetics
Radiation, Ionizing
Signal Transduction
/ genetics
Trans-Activators
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 10 2020
30 10 2020
Historique:
received:
18
10
2019
accepted:
13
10
2020
entrez:
31
10
2020
pubmed:
1
11
2020
medline:
2
3
2021
Statut:
epublish
Résumé
Human glioblastoma (GBM) is the most common primary malignant brain tumor. A minor subpopulation of cancer cells, known as glioma stem-like cells (GSCs), are thought to play a major role in tumor relapse due to their stem cell-like properties, their high resistance to conventional treatments and their high invasion capacity. We show that ionizing radiation specifically enhances the motility and invasiveness of human GSCs through the stabilization and nuclear accumulation of the hypoxia-inducible factor 1α (HIF1α), which in turn transcriptionally activates the Junction-mediating and regulatory protein (JMY). Finally, JMY accumulates in the cytoplasm where it stimulates GSC migration via its actin nucleation-promoting activity. Targeting JMY could thus open the way to the development of new therapeutic strategies to improve the efficacy of radiotherapy and prevent glioma recurrence.
Identifiants
pubmed: 33128011
doi: 10.1038/s41598-020-75300-5
pii: 10.1038/s41598-020-75300-5
pmc: PMC7603339
doi:
Substances chimiques
Hypoxia-Inducible Factor 1, alpha Subunit
0
JMY protein, human
0
Nuclear Proteins
0
Trans-Activators
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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