Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma
| Autor: | Grégoire Quinet, Wendy Xolalpa, Diana Reyes-Garau, Núria Profitós-Pelejà, Mikel Azkargorta, Laurie Ceccato, Maria Gonzalez-Santamarta, Maria Marsal, Jordi Andilla, Fabienne Aillet, Francesc Bosch, Felix Elortza, Pablo Loza-Alvarez, Brigitte Sola, Olivier Coux, Rune Matthiesen, Gaël Roué, Manuel S. Rodriguez |
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| Přispěvatelé: | Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Cell Biology and Stem Cells Unit (CICbioGUNE), Technologic Park of Bizkaia, Josep Carreras Leukaemia Research Institute (IJC), Barcelona Institute of Science and Technology (BIST), Institut de Ciencies Fotoniques [Castelldefels] (ICFO), Vall d'Hebron University Hospital [Barcelona], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Spanish MINECO, CTQ2011–27874 grant, UbiCODE project - Marie Skłodowska-Curie grant agreement No 765445, Institut National du Cancer, France (PLBIO16-251), CONACyT-SRE (Mexico) grant 0280365, REPERE program of Occitanie, La Ligue contre le cancer du Gard, Spanish MINECO 'Severo Ochoa' program for Centres of Excellence in R&D (CEX2019-000910-S [MCIN/ AEI/10.13039/501100011033]), Sola, Brigitte, Institut Català de la Salut, [Quinet G, Ceccato L] Laboratoire de Chimie de Coordination (LCC) CNRS-UPR8241, UPS, Toulouse, France. [Xolalpa W] Proteomics Unit, CIC bioGUNE, Parque Tecnológico de Bizkaia, Derio, Spain. [Reyes-Garau D, Profitós-Pelejà N] Lymphoma Translational Group, UBIRed, Josep Carreras Leukaemia Research Institute, Badalona, Spain. [Azkargorta M] Proteomics Platform CICbioGUNE, Basque Research and Technology Alliance (BRTA), CIBERehd, ProteoRed-ISCIII, Parque Tecnológico de Bizkaia, Derio, Spain. [Bosch F] Laboratory of Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Centro de Estudos de Doenças Crónicas (CEDOC) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology
autophagy Cancer Research ubiquitin proteome Enzims proteolítics - Inhibidors Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] [SDV.CAN]Life Sciences [q-bio]/Cancer Apoptosis [SDV.BC]Life Sciences [q-bio]/Cellular Biology Other subheadings::Other subheadings::/drug therapy [Other subheadings] SDG 3 - Good Health and Well-being [SDV.CAN] Life Sciences [q-bio]/Cancer [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Autophagy Proteasome inhibitor neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células del manto [ENFERMEDADES] apoptosis proteasome inhibitor TUBEs verteporfin [SDV.BC] Life Sciences [q-bio]/Cellular Biology Verteporfin [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology Ubiquitin proteome Oncology Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma Non-Hodgkin::Lymphoma Mantle-Cell [DISEASES] [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Sistema limfàtic - Càncer - Tractament |
| Zdroj: | Cancers Cancers, 2022, 14 (4), pp.923. ⟨10.3390/cancers14040923⟩ Cancers; Volume 14; Issue 4; Pages: 923 Scientia r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname |
| ISSN: | 2072-6694 |
| Popis: | Apoptosis; Autophagy; Proteasome inhibitor Apoptosis; Autofagia; Inhibidor del proteasoma Apoptosi; Autofàgia; Inhibidor del proteasoma Protein ubiquitylation coordinates crucial cellular events in physiological and pathological conditions. A comparative analysis of the ubiquitin proteome from bortezomib (BTZ)-sensitive and BTZ-resistant mantle cell lymphoma (MCL) revealed an enrichment of the autophagy–lysosome system (ALS) in BTZ-resistant cells. Pharmacological inhibition of autophagy at the level of lysosome-fusion revealed a constitutive activation of proteaphagy and accumulation of proteasome subunits within autophagosomes in different MCL cell lines with acquired or natural resistance to BTZ. Inhibition of the autophagy receptor p62/SQSTM1 upon verteporfin (VTP) treatment disrupted proteaphagosome assembly, reduced co-localization of proteasome subunits with autophagy markers and negatively impacted proteasome activity. Finally, the silencing or pharmacological inhibition of p62 restored the apoptosis threshold at physiological levels in BTZ-resistant cells both in vitro and in vivo. In total, these results demonstrate for the first time a proteolytic switch from the ubiquitin–proteasome system (UPS) to ALS in B-cell lymphoma refractory to proteasome inhibition, pointing out a crucial role for proteaphagy in this phenomenon and paving the way for the design of alternative therapeutic venues in treatment-resistant tumors. This work was supported at early stages by Spanish MINECO, CTQ2011–27874 grant. M.G.-S. is a fellow of the UbiCODE project funded by the EU’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 765445. M.S.R. and L.C. were also funded by the Institut National du Cancer, France (PLBIO16-251), CONACyT-SRE (Mexico) grant 0280365 and the REPERE program of Occitanie. O.C. is funded by “La Ligue contre le cancer du Gard”. ICFO authors were supported by funding from the Spanish MINECO “Severo Ochoa” program for Centres of Excellence in R&D (CEX2019-000910-S [MCIN/ AEI/10.13039/501100011033]), from Fundació Privada Cellex, Fundación Mig-Puig, from Generalitat de Catalunya CERCA program and from LASERLAB Europe (grant agreement No 871124;). G.R. was financially supported by Fondo de Investigación Sanitaria PI15/00102 and PI18/01383, European Regional Development Fund (ERDF) ‘Una manera de hacer Europa’. G.R. and D.R.G. are members of the Spanish Network of Excellence UBIRed funded by the Spanish Ministry Science, Innovation and Universities (SAF2017-90900-REDT). |
| Databáze: | OpenAIRE |
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