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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988805/ https://www.ncbi.nlm.nih.gov/pubmed/24699711 http://dx.doi.org/10.1038/ncomms4608 |
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author | Lopez-Serra, Paula Marcilla, Miguel Villanueva, Alberto Ramos-Fernandez, Antonio Palau, Anna Leal, Lucía Wahi, Jessica E. Setien-Baranda, Fernando Szczesna, Karolina Moutinho, Catia Martinez-Cardus, Anna Heyn, Holger Sandoval, Juan Puertas, Sara Vidal, August Sanjuan, Xavier Martinez-Balibrea, Eva Viñals, Francesc Perales, Jose C. Bramsem, Jesper B. Ørntoft, Torben F. Andersen, Claus L. Tabernero, Josep McDermott, Ultan Boxer, Matthew B. Heiden, Matthew G. Vander Albar, Juan Pablo Esteller, Manel |
author_facet | Lopez-Serra, Paula Marcilla, Miguel Villanueva, Alberto Ramos-Fernandez, Antonio Palau, Anna Leal, Lucía Wahi, Jessica E. Setien-Baranda, Fernando Szczesna, Karolina Moutinho, Catia Martinez-Cardus, Anna Heyn, Holger Sandoval, Juan Puertas, Sara Vidal, August Sanjuan, Xavier Martinez-Balibrea, Eva Viñals, Francesc Perales, Jose C. Bramsem, Jesper B. Ørntoft, Torben F. Andersen, Claus L. Tabernero, Josep McDermott, Ultan Boxer, Matthew B. Heiden, Matthew G. Vander Albar, Juan Pablo Esteller, Manel |
author_sort | Lopez-Serra, Paula |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3988805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-39888052014-04-18 A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect Lopez-Serra, Paula Marcilla, Miguel Villanueva, Alberto Ramos-Fernandez, Antonio Palau, Anna Leal, Lucía Wahi, Jessica E. Setien-Baranda, Fernando Szczesna, Karolina Moutinho, Catia Martinez-Cardus, Anna Heyn, Holger Sandoval, Juan Puertas, Sara Vidal, August Sanjuan, Xavier Martinez-Balibrea, Eva Viñals, Francesc Perales, Jose C. Bramsem, Jesper B. Ørntoft, Torben F. Andersen, Claus L. Tabernero, Josep McDermott, Ultan Boxer, Matthew B. Heiden, Matthew G. Vander Albar, Juan Pablo Esteller, Manel Nat Commun Article 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. Nature Pub. Group 2014-04-03 /pmc/articles/PMC3988805/ /pubmed/24699711 http://dx.doi.org/10.1038/ncomms4608 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Article Lopez-Serra, Paula Marcilla, Miguel Villanueva, Alberto Ramos-Fernandez, Antonio Palau, Anna Leal, Lucía Wahi, Jessica E. Setien-Baranda, Fernando Szczesna, Karolina Moutinho, Catia Martinez-Cardus, Anna Heyn, Holger Sandoval, Juan Puertas, Sara Vidal, August Sanjuan, Xavier Martinez-Balibrea, Eva Viñals, Francesc Perales, Jose C. Bramsem, Jesper B. Ørntoft, Torben F. Andersen, Claus L. Tabernero, Josep McDermott, Ultan Boxer, Matthew B. Heiden, Matthew G. Vander Albar, Juan Pablo Esteller, Manel 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 |
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_short | A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect |
title_sort | derl3-associated defect in the degradation of slc2a1 mediates the warburg effect |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988805/ https://www.ncbi.nlm.nih.gov/pubmed/24699711 http://dx.doi.org/10.1038/ncomms4608 |
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