Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma

Apoptosis; Autophagy; Proteasome inhibitor

Detalles Bibliográficos
Autores: Quinet, Grégoire, Xolalpa, Wendy, Reyes Garau, Diana, Azkargorta, Mikel, Ceccato, Laurie, Profitós-Pelejà, Núria, Bosch, Francesc
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Departament de Salut de la Generalitat de Catalunya (DS)
Repositorio:Scientia. Dipòsit d'Informació Digital del Departament de Salut
OAI Identifier:oai:scientiasalut.gencat.cat:11351/7853
Acceso en línea:https://hdl.handle.net/11351/7853
Access Level:acceso abierto
Palabra clave:Sistema limfàtic - Càncer - Tractament
Enzims proteolítics - Inhibidors
DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, Mantle-Cell
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células del manto
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma
title Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma
spellingShingle Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma
Quinet, Grégoire
Sistema limfàtic - Càncer - Tractament
Enzims proteolítics - Inhibidors
DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, Mantle-Cell
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células del manto
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
title_short Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma
title_full Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma
title_fullStr Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma
title_full_unstemmed Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma
title_sort Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell Lymphoma
dc.creator.none.fl_str_mv Quinet, Grégoire
Xolalpa, Wendy
Reyes Garau, Diana
Azkargorta, Mikel
Ceccato, Laurie
Profitós-Pelejà, Núria
Bosch, Francesc
author Quinet, Grégoire
author_facet Quinet, Grégoire
Xolalpa, Wendy
Reyes Garau, Diana
Azkargorta, Mikel
Ceccato, Laurie
Profitós-Pelejà, Núria
Bosch, Francesc
author_role author
author2 Xolalpa, Wendy
Reyes Garau, Diana
Azkargorta, Mikel
Ceccato, Laurie
Profitós-Pelejà, Núria
Bosch, Francesc
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv 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
dc.subject.none.fl_str_mv Sistema limfàtic - Càncer - Tractament
Enzims proteolítics - Inhibidors
DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, Mantle-Cell
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células del manto
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
topic Sistema limfàtic - Càncer - Tractament
Enzims proteolítics - Inhibidors
DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, Mantle-Cell
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células del manto
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
description Apoptosis; Autophagy; Proteasome inhibitor
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/7853
url https://hdl.handle.net/11351/7853
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cancers;14(4)
https://doi.org/10.3390/cancers14040923
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Scientia
reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname:Departament de Salut de la Generalitat de Catalunya (DS)
instname_str Departament de Salut de la Generalitat de Catalunya (DS)
reponame_str Scientia. Dipòsit d'Informació Digital del Departament de Salut
collection Scientia. Dipòsit d'Informació Digital del Departament de Salut
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869417664977305600
spelling Constitutive Activation of p62/Sequestosome-1-Mediated Proteaphagy Regulates Proteolysis and Impairs Cell Death in Bortezomib-Resistant Mantle Cell LymphomaQuinet, GrégoireXolalpa, WendyReyes Garau, DianaAzkargorta, MikelCeccato, LaurieProfitós-Pelejà, NúriaBosch, FrancescSistema limfàtic - Càncer - TractamentEnzims proteolítics - InhibidorsDISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, Mantle-CellOther subheadings::Other subheadings::Other subheadings::/drug therapyENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células del mantoOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaApoptosis; Autophagy; Proteasome inhibitorApoptosis; Autofagia; Inhibidor del proteasomaApoptosi; Autofàgia; Inhibidor del proteasomaProtein 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).MDPIInstitut 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, SpainVall d'Hebron Barcelona Hospital Campus202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/7853Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésCancers;14(4)https://doi.org/10.3390/cancers14040923Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/78532026-06-12T09:38:37Z
score 15.811543

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