[PDF][PDF] Cilium induction triggers differentiation of glioma stem cells

G Goranci-Buzhala, A Mariappan, L Ricci-Vitiani… - Cell reports, 2021 - cell.com
G Goranci-Buzhala, A Mariappan, L Ricci-Vitiani, N Josipovic, S Pacioni, M Gottardo, J Ptok
Cell reports, 2021cell.com
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 …
Summary
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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