Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis

Marie C. Matrka, Miki Watanabe, Ranjithmenon Muraleedharan, Paul F. Lambert, Andrew N. Lane, Lindsey E. Romick-Rosendale, Susanne I. Wells

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos). To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA) that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth.

Original languageEnglish
Article numbere0177952
JournalPLoS ONE
Issue number5
StatePublished - May 2017

Bibliographical note

Funding Information:
Funding: This work was supported by the National Institutes of Health R01-CA116316 to S.I.W.; the University of Cincinnati Cancer Institute Head & Neck Comprehensive Center Pilot Grant Program 2014; Carmen L. Buck endowment (to ANL) and National Institutes of Health 1U24DK097215-01A1 to ANL. All flow cytometric data were acquired using the Research Flow Cytometry Core in the Division of Rheumatology at Cincinnati Children’s Hospital Medical Center and supported in part by the Digestive Health Center NIDDK P30 DK078392. All NMR-based metabolomics data was acquired and analyzed within the NMR-Based Metabolomics Core, a Cincinnati Children’s Research Foundation Shared Facility, in the Division of Pathology and Laboratory Medicine at CCHMC. We thank Dr. James Lessard for the monoclonal actin antibody, and Eric Smith, Lisa Privette-Vinnedge, Allie Adams, and Elizabeth Hoskins for proofreading and editing.

Publisher Copyright:
© 2017 Matrka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Agricultural and Biological Sciences (all)
  • General


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