A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
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Lopez-Serra-2014-DERL3-associated Defect.pdf
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Author(s)
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
Date Issued
April 2014
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
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).
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1038/ncomms4608
