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.

Goranci-Buzhala, G., Mariappan, A., Ricci-Vitiani, L., Josipovic, N., Pacioni, S., Gottardo, M., et al. (2021). Cilium induction triggers differentiation of glioma stem cells. CELL REPORTS, 36(10) [10.1016/j.celrep.2021.109656].

Cilium induction triggers differentiation of glioma stem cells

Gottardo, Marco;Callaini, Giuliano;
2021-01-01

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.
2021
Goranci-Buzhala, G., Mariappan, A., Ricci-Vitiani, L., Josipovic, N., Pacioni, S., Gottardo, M., et al. (2021). Cilium induction triggers differentiation of glioma stem cells. CELL REPORTS, 36(10) [10.1016/j.celrep.2021.109656].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1281035