Universität zu Köln

Goranci-Buzhala, Gladiola, Mariappan, Aruljothi, Ricci-Vitiani, Lucia, Josipovic, Natasa ORCID: 0000-0001-7683-0869, Pacioni, Simone, Gottardo, Marco, Ptok, Johannes, Schaal, Heiner, Callaini, Giuliano, Rajalingam, Krishnaraj, Dynlacht, Brian, Hadian, Kamyar ORCID: 0000-0001-8727-2575, Papantonis, Argyris, Pallini, Roberto and Gopalakrishnan, Jay (2021). Cilium induction triggers differentiation of glioma stem cells. Cell Reports, 36 (10). CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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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-a) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Goranci-Buzhala, Gladiola UNSPECIFIED UNSPECIFIED UNSPECIFIED Mariappan, Aruljothi UNSPECIFIED UNSPECIFIED UNSPECIFIED Ricci-Vitiani, Lucia UNSPECIFIED UNSPECIFIED UNSPECIFIED Josipovic, Natasa UNSPECIFIED orcid.org/0000-0001-7683-0869 UNSPECIFIED Pacioni, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Gottardo, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Ptok, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaal, Heiner UNSPECIFIED UNSPECIFIED UNSPECIFIED Callaini, Giuliano UNSPECIFIED UNSPECIFIED UNSPECIFIED Rajalingam, Krishnaraj UNSPECIFIED UNSPECIFIED UNSPECIFIED Dynlacht, Brian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hadian, Kamyar UNSPECIFIED orcid.org/0000-0001-8727-2575 UNSPECIFIED Papantonis, Argyris UNSPECIFIED UNSPECIFIED UNSPECIFIED Pallini, Roberto UNSPECIFIED UNSPECIFIED UNSPECIFIED Gopalakrishnan, Jay UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-600540
DOI:	10.1016/j.celrep.2021.109656
Journal or Publication Title:	Cell Reports
Volume:	36
Number:	10
Date:	2021
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PATIENT-DERIVED GLIOBLASTOMA; CILIOGENESIS; IDENTIFICATION; TEMOZOLOMIDE; ACTIVATION; SUBTYPES; NEURONS; AURORA; PDGFRA; GROWTH Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60054