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Goranci-Buzhala, G.* ; Mariappan, A.* ; Ricci-Vitiani, L.* ; Josipovic, N.* ; Pacioni, S.* ; Gottardo, M.* ; Ptok, J.* ; Schaal, H.* ; Callaini, G.* ; Rajalingam, K.* ; Dynlacht, B.D.* ; Hadian, K. ; Papantonis, A.* ; Pallini, R.* ; Gopalakrishnan, J.*

Cilium induction triggers differentiation of glioma stem cells.

Cell Rep. 36:109656 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Brain Organoids ; Cell Cycle ; Cilium Checkpoint ; Confocal 3d Imaging ; Glioblastoma ; Invasion Assay ; Primary Cilium ; Tissue Clearing; Patient-derived Glioblastoma; Ciliogenesis; Identification; Temozolomide; Activation; Subtypes; Neurons; Aurora; Pdgfra; Growth
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 36, Issue: 10, Pages: , Article Number: 109656 Supplement: ,
Publisher Cell Press
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOXI)
Grants SPP1935
Pharmacology and Bayer Graduate Program at the University of Cologne
AIRC
Deutsche Krebshilfe