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Cilium induction triggers differentiation of glioma stem cells.
- Source :
-
Cell reports [Cell Rep] 2021 Sep 07; Vol. 36 (10), pp. 109656. - Publication Year :
- 2021
-
Abstract
- Glioblastoma multiforme (GBM) possesses glioma stem cells (GSCs) that promote self-renewal, tumor propagation, and relapse. Understanding the mechanisms of GSCs self-renewal can offer targeted therapeutic interventions. However, insufficient knowledge of GSCs' fundamental biology is a significant bottleneck hindering these efforts. Here, we show that patient-derived GSCs recruit elevated levels of proteins that ensure the temporal cilium disassembly, leading to suppressed ciliogenesis. Depleting the cilia disassembly complex components is sufficient to induce ciliogenesis in a subset of GSCs via relocating platelet-derived growth factor receptor-alpha (PDGFR-α) to a newly induced cilium. Importantly, restoring ciliogenesis enabled GSCs to switch from self-renewal to differentiation. Finally, using an organoid-based glioma invasion assay and brain xenografts in mice, we establish that ciliogenesis-induced differentiation can prevent the infiltration of GSCs into the brain. Our findings illustrate a role for cilium as a molecular switch in determining GSCs' fate and suggest cilium induction as an attractive strategy to intervene in GSCs proliferation.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Brain metabolism
Brain pathology
Cell Line, Tumor
Cell Proliferation physiology
Cell Self Renewal physiology
Glioblastoma pathology
Humans
Mice
Neoplastic Stem Cells metabolism
Brain Neoplasms pathology
Cell Differentiation physiology
Glioma pathology
Neoplasm Recurrence, Local pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 36
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 34496239
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.109656