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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Detalles Bibliográficos
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 recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/125908
Acceso en línea:https://hdl.handle.net/2445/125908
Access Level:acceso abierto
Palabra clave:Cèl·lules canceroses
Oncologia
Cancer cells
Oncology
Descripción
Sumario: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.

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