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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)
Verlagsversion 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Cell Reports
Quellenangaben Band: 36, Heft: 10, Seiten: , Artikelnummer: 109656 Supplement: ,
Verlag Cell Press
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Toxicology and Pharmacology (TOXI)
Förderungen SPP1935
Pharmacology and Bayer Graduate Program at the University of Cologne
AIRC
Deutsche Krebshilfe