The HIF1α/JMY pathway promotes glioblastoma stem-like cell invasiveness after irradiation

• Published in: Scientific reports Vol. 10; no. 1; p. 18742
• Main Authors: Gauthier, Laurent R., Saati, Mahasen, Bensalah-Pigeon, Hayet, Ben M’Barek, Karim, Gitton-Quent, Oscar, Bertrand, Romane, Busso, Didier, Mouthon, Marc-André, Collura, Ada, Junier, Marie-Pierre, Chneiweiss, Hervé, Pineda, José R., Boussin, François D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.10.2020; Nature Publishing Group
• Subjects: 631/532/71; 631/67/1922; 631/80/128/1276; 631/80/84/2336; Actin; Brain cancer; Brain tumors; Cell Line, Tumor; Cell Movement - genetics; Cell Movement - radiation effects; Cell Nucleus - metabolism; Cell Nucleus - radiation effects; Cytoplasm; Cytoplasm - metabolism; Cytoplasm - radiation effects; Glioblastoma; Glioblastoma - metabolism; Glioblastoma - pathology; Glioma; Glioma - metabolism; Glioma - pathology; Glioma cells; Humanities and Social Sciences; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factor 1a; Hypoxia-inducible factors; Invasiveness; Ionizing radiation; Irradiation; Life Sciences; multidisciplinary; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Radiation therapy; Radiation, Ionizing; Science; Science (multidisciplinary); Signal Transduction - genetics; Signal Transduction - radiation effects; Stem cells; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-75300-5

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.