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RESEARCH PRODUCT
Cilium induction triggers differentiation of glioma stem cells.
Argyris PapantonisKamyar HadianAruljothi MariappanKrishnaraj RajalingamLucia Ricci-vitianiJay GopalakrishnanBrian David DynlachtHeiner SchaalNatasa JosipovicMarco GottardoJohannes PtokGiuliano CallainiRoberto PalliniGladiola Goranci-buzhalaSimone Pacionisubject
endocrine systemmedicine.medical_treatmentBiologyGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesMice0302 clinical medicineGentamicin protection assayGliomaCiliogenesisCell Line TumormedicineAnimalsHumansCell Self Renewal030304 developmental biologyCell Proliferation0303 health sciencesBrain NeoplasmsCiliumGrowth factorfungiBrainCell DifferentiationGliomaCilium disassemblyCell cyclemedicine.diseaseCell biology030220 oncology & carcinogenesisNeoplastic Stem CellsStem cellNeoplasm Recurrence LocalGlioblastomadescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-03-06 | Cell reports |