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Children's Cancer Institute Lowy Canc... 1 Department of Experimental Oncology I... 1 Department of Oncology and Hemato Onc... 1 IFOM Milan Italy 1 Institute for Clinical Chemistry and ... 1 Institute of Biomedicine University o... 1 Laboratory of Cancer Cell Biology Ins... 1 Medical Clinic 1 University Hospital ... 1 Mildred Scheel Early Career Center Na... 1 School of Biomedical Sciences UNSW Sy... 1 Turku Bioscience Centre University of... 1
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Children's Cancer Institute Lowy Canc... 1 Department of Experimental Oncology I... 1 Department of Oncology and Hemato Onc... 1 IFOM Milan Italy 1 Institute for Clinical Chemistry and ... 1 Institute of Biomedicine University o... 1 Laboratory of Cancer Cell Biology Ins... 1 Medical Clinic 1 University Hospital ... 1 Mildred Scheel Early Career Center Na... 1 School of Biomedical Sciences UNSW Sy... 1 Turku Bioscience Centre University of... 1
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- Cazzoli, Riccardo
- Romeo, Francesco
- Pallavicini, Isabella
- Peri, Sebastiano
- Romanenghi, Mauro
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Pérez-Valencia, Juan Alberto
Autor Pérez-Valencia, Juan Alberto Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany Medical Clinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Mildred-Scheel Early Career Center, National Center for Tumor Diseases Dresden (NCT/UCC) University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
- Hagag, Eman
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Ferrucci, Filippo
Autor Ferrucci, Filippo Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany Medical Clinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Mildred-Scheel Early Career Center, National Center for Tumor Diseases Dresden (NCT/UCC) University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
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Elgendy, Mohamed
Autor Elgendy, Mohamed Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany Medical Clinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Mildred-Scheel Early Career Center, National Center for Tumor Diseases Dresden (NCT/UCC) University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany Laboratory of Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
- Vittorio, Orazio
NLK
Cell Press Free Archives
od 2012
Directory of Open Access Journals
od 2012
Free Medical Journals
od 2012
Freely Accessible Science Journals
od 2012-01-26
Open Access Digital Library
od 2012-01-26
Open Access Digital Library
od 2012-01-01
Elsevier Open Access Journals
od 2012-01-26
PubMed
37289585
DOI
10.1016/j.celrep.2023.112616
Knihovny.cz E-zdroje
Combined inhibition of oxidative phosphorylation (OXPHOS) and glycolysis has been shown to activate a PP2A-dependent signaling pathway, leading to tumor cell death. Here, we analyze highly selective mitochondrial complex I or III inhibitors in vitro and in vivo to elucidate the molecular mechanisms leading to cell death following OXPHOS inhibition. We show that IACS-010759 treatment (complex I inhibitor) induces a reactive oxygen species (ROS)-dependent dissociation of CIP2A from PP2A, leading to its destabilization and degradation through chaperone-mediated autophagy. Mitochondrial complex III inhibition has analogous effects. We establish that activation of the PP2A holoenzyme containing B56δ regulatory subunit selectively mediates tumor cell death, while the arrest in proliferation that is observed upon IACS-010759 treatment does not depend on the PP2A-B56δ complex. These studies provide a molecular characterization of the events subsequent to the alteration of critical bioenergetic pathways and help to refine clinical studies aimed to exploit metabolic vulnerabilities of tumor cells.
- MeSH
- autoantigeny metabolismus MeSH
- autofagie zprostředkovaná chaperony * MeSH
- energetický metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory * patologie MeSH
- oxidativní fosforylace MeSH
- proteinfosfatasa 2 antagonisté a inhibitory metabolismus MeSH
- respirační komplex I * antagonisté a inhibitory MeSH
- signální transdukce MeSH
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- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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