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Inhibition of mitoc...
Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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Elsevier BV,2021
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:su-193707
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-193707URI
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https://doi.org/10.1016/j.celrep.2021.109024DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:146531124URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Glioblastoma stem cells (GSCs) resist current glioblastoma (GBM) therapies. GSCs rely highly on oxidative phosphorylation (OXPHOS), whose function requires mitochondrial translation. Here we explore the therapeutic potential of targeting mitochondrial translation and report the results of high-content screening with putative blockers of mitochondrial ribosomes. We identify the bacterial antibiotic quinupristin/dalfopristin (Q/D) as an effective suppressor of GSC growth. Q/D also decreases the clonogenicity of GSCs in vitro, consequently dysregulating the cell cycle and inducing apoptosis. Cryoelectron microscopy (cryo-EM) reveals that Q/D binds to the large mitoribosomal subunit, inhibiting mitochondrial protein synthesis and functionally dysregulating OXPHOS complexes. These data suggest that targeting mitochondrial translation could be explored to therapeutically suppress GSC growth in GBM and that Q/D could potentially be repurposed for cancer treatment.
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Notarangelo, Michela
(author)
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Aibara, ShintaroStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)(Swepub:su)saiba
(author)
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Re, Angela
(author)
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Ricci, Gianluca
(author)
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Guida, Marianna
(author)
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Soldano, Alessia
(author)
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Adami, Valentina
(author)
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Ambrosini, Chiara
(author)
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Broso, Francesca
(author)
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Rosatti, Emanuele Filiberto
(author)
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Longhi, Sara
(author)
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Buccarelli, Mariachiara
(author)
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D'Alessandris, Quintino G.
(author)
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Giannetti, Stefano
(author)
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Pacioni, Simone
(author)
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Ricci-Vitiani, Lucia
(author)
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Rorbach, JoannaKarolinska Institutet
(author)
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Pallini, Roberto
(author)
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Roulland, Sandrine
(author)
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Amunts, AlexeyStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)(Swepub:su)aamun
(author)
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Mancini, Ines
(author)
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Modelska, Angelika
(author)
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Quattrone, Alessandro
(author)
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Stockholms universitetInstitutionen för biokemi och biofysik
(creator_code:org_t)
Related titles
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In:Cell Reports: Elsevier BV35:42211-1247
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Sighel, Denise
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Notarangelo, Mic ...
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Aibara, Shintaro
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Re, Angela
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Ricci, Gianluca
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Guida, Marianna
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Soldano, Alessia
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Adami, Valentina
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Ambrosini, Chiar ...
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Broso, Francesca
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Rosatti, Emanuel ...
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Longhi, Sara
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Buccarelli, Mari ...
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D'Alessandris, Q ...
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Giannetti, Stefa ...
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Pacioni, Simone
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Ricci-Vitiani, L ...
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Rorbach, Joanna
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Pallini, Roberto
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Roulland, Sandri ...
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Amunts, Alexey
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Mancini, Ines
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Modelska, Angeli ...
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Quattrone, Aless ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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Cell Reports
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Stockholm University
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Karolinska Institutet