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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/1721.1/96845 https://orcid.org/0000-0002-6702-4192 |
| _version_ | 1811071763917832192 |
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| author | Lopez-Serra, Paula Marcilla, Miguel Villanueva, Alberto Ramos-Fernandez, Antonio Palau, Anna 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. Andersen, Claus L. Tabernero, Josep McDermott, Ultan Boxer, Matthew B. Albar, Juan Pablo Esteller, Manel Vander Heiden, Matthew G. Leal, Lucia Orntoft, Torben F. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Lopez-Serra, Paula Marcilla, Miguel Villanueva, Alberto Ramos-Fernandez, Antonio Palau, Anna 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. Andersen, Claus L. Tabernero, Josep McDermott, Ultan Boxer, Matthew B. Albar, Juan Pablo Esteller, Manel Vander Heiden, Matthew G. Leal, Lucia Orntoft, Torben F. |
| author_sort | Lopez-Serra, Paula |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T08:55:51Z |
| format | Article |
| id | mit-1721.1/96845 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:55:51Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/968452022-09-30T12:14:01Z 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 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. Andersen, Claus L. Tabernero, Josep McDermott, Ultan Boxer, Matthew B. Albar, Juan Pablo Esteller, Manel Vander Heiden, Matthew G. Leal, Lucia Orntoft, Torben F. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Vander Heiden, Matthew G. 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. Seventh Framework Programme (European Commission) (Grant HEALTH-F5-2010-258236-SYSCOL) Seventh Framework Programme (European Commission) (Grant HEALTH-F2-2011-259015-COLTHERES) Cellex Foundation Olga Torres Foundation European Research Council (EPINORC Project Grant Agreement 268626) Spain. Ministerio de Economia y Competividad (MINECO Project SAF2011-22803) Institute of Health Carlos III (RTICC Grant RD12/0036/0039) 2015-04-29T15:51:51Z 2015-04-29T15:51:51Z 2014-04 2013-10 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/96845 Lopez-Serra, Paula, Miguel Marcilla, Alberto Villanueva, Antonio Ramos-Fernandez, Anna Palau, Lucía Leal, Jessica E. Wahi, et al. “A DERL3-Associated Defect in the Degradation of SLC2A1 Mediates the Warburg Effect.” Nature Communications 5 (April 3, 2014). https://orcid.org/0000-0002-6702-4192 en_US http://dx.doi.org/10.1038/ncomms4608 Nature Communications Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf Nature Publishing Group Nature Publishing Group |
| spellingShingle | Lopez-Serra, Paula Marcilla, Miguel Villanueva, Alberto Ramos-Fernandez, Antonio Palau, Anna 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. Andersen, Claus L. Tabernero, Josep McDermott, Ultan Boxer, Matthew B. Albar, Juan Pablo Esteller, Manel Vander Heiden, Matthew G. Leal, Lucia Orntoft, Torben F. 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 |
| url | http://hdl.handle.net/1721.1/96845 https://orcid.org/0000-0002-6702-4192 |
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