A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect

Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protei...

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Autores: López Serra, Paula, Marcilla, Miguel, Villanueva Garatachea, Alberto, Ramos Fernandez, Antonio, Palau, Anna, Leal, Lucía, Wahi, Jessica E., Setién, Fernando, Szczesna, Karolina, Moutinho, Cátia, Martínez Cardús, Anna, Heyn, Holger, Sandoval, Juan, Puertas, Sara, Vidal-Bel, August, Sanjuan, Xavier, Martínez Balibrea, Eva, Viñals Canals, Francesc, Perales Losa, Carlos, Bramsem, Jesper B., Ørntoft, Torben F., Andersen, Claus L., Tabernero Caturla, Josep, McDermott, Ultan, Boxer, Matthew B., Vander Heiden, Matthew G., Albar, Juan Pablo, Esteller, Manel, 1968-
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2014
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/125908
Acesso em linha:https://hdl.handle.net/2445/125908
Access Level:Acceso aberto
Palavra-chave:Cèl·lules canceroses
Oncologia
Cancer cells
Oncology
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spelling A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effectLópez Serra, PaulaMarcilla, MiguelVillanueva Garatachea, AlbertoRamos Fernandez, AntonioPalau, AnnaLeal, LucíaWahi, Jessica E.Setién, FernandoSzczesna, KarolinaMoutinho, CátiaMartínez Cardús, AnnaHeyn, HolgerSandoval, JuanPuertas, SaraVidal-Bel, AugustSanjuan, XavierMartínez Balibrea, EvaViñals Canals, FrancescPerales Losa, CarlosBramsem, Jesper B.Ørntoft, Torben F.Andersen, Claus L.Tabernero Caturla, JosepMcDermott, UltanBoxer, Matthew B.Vander Heiden, Matthew G.Albar, Juan PabloEsteller, Manel, 1968-Cèl·lules cancerosesOncologiaCancer cellsOncologyCancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis.Nature Publishing Group2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/125908Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/ncomms4608Nature Communications, 2014, vol. 5https://doi.org/10.1038/ncomms4608info:eu-repo/grantAgreement/EC/FP7/268626info:eu-repo/grantAgreement/EC/FP7/259015cc by (c) López Serra et al., 2014http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1259082026-05-27T06:46:51Z
dc.title.none.fl_str_mv A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
title A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
spellingShingle A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
López Serra, Paula
Cèl·lules canceroses
Oncologia
Cancer cells
Oncology
title_short A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
title_full A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
title_fullStr A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
title_full_unstemmed A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
title_sort A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
dc.creator.none.fl_str_mv López Serra, Paula
Marcilla, Miguel
Villanueva Garatachea, Alberto
Ramos Fernandez, Antonio
Palau, Anna
Leal, Lucía
Wahi, Jessica E.
Setién, Fernando
Szczesna, Karolina
Moutinho, Cátia
Martínez Cardús, Anna
Heyn, Holger
Sandoval, Juan
Puertas, Sara
Vidal-Bel, August
Sanjuan, Xavier
Martínez Balibrea, Eva
Viñals Canals, Francesc
Perales Losa, Carlos
Bramsem, Jesper B.
Ørntoft, Torben F.
Andersen, Claus L.
Tabernero Caturla, Josep
McDermott, Ultan
Boxer, Matthew B.
Vander Heiden, Matthew G.
Albar, Juan Pablo
Esteller, Manel, 1968-
author López Serra, Paula
author_facet López Serra, Paula
Marcilla, Miguel
Villanueva Garatachea, Alberto
Ramos Fernandez, Antonio
Palau, Anna
Leal, Lucía
Wahi, Jessica E.
Setién, Fernando
Szczesna, Karolina
Moutinho, Cátia
Martínez Cardús, Anna
Heyn, Holger
Sandoval, Juan
Puertas, Sara
Vidal-Bel, August
Sanjuan, Xavier
Martínez Balibrea, Eva
Viñals Canals, Francesc
Perales Losa, Carlos
Bramsem, Jesper B.
Ørntoft, Torben F.
Andersen, Claus L.
Tabernero Caturla, Josep
McDermott, Ultan
Boxer, Matthew B.
Vander Heiden, Matthew G.
Albar, Juan Pablo
Esteller, Manel, 1968-
author_role author
author2 Marcilla, Miguel
Villanueva Garatachea, Alberto
Ramos Fernandez, Antonio
Palau, Anna
Leal, Lucía
Wahi, Jessica E.
Setién, Fernando
Szczesna, Karolina
Moutinho, Cátia
Martínez Cardús, Anna
Heyn, Holger
Sandoval, Juan
Puertas, Sara
Vidal-Bel, August
Sanjuan, Xavier
Martínez Balibrea, Eva
Viñals Canals, Francesc
Perales Losa, Carlos
Bramsem, Jesper B.
Ørntoft, Torben F.
Andersen, Claus L.
Tabernero Caturla, Josep
McDermott, Ultan
Boxer, Matthew B.
Vander Heiden, Matthew G.
Albar, Juan Pablo
Esteller, Manel, 1968-
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules canceroses
Oncologia
Cancer cells
Oncology
topic Cèl·lules canceroses
Oncologia
Cancer cells
Oncology
description Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis.
publishDate 2014
dc.date.none.fl_str_mv 2014
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/2445/125908
url https://hdl.handle.net/2445/125908
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/ncomms4608
Nature Communications, 2014, vol. 5
https://doi.org/10.1038/ncomms4608
info:eu-repo/grantAgreement/EC/FP7/268626
info:eu-repo/grantAgreement/EC/FP7/259015
dc.rights.none.fl_str_mv cc by (c) López Serra et al., 2014
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) López Serra et al., 2014
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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