PMID- 28558019
OWN - NLM
STAT- MEDLINE
DCOM- 20170921
LR  - 20240214
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 5
DP  - 2017
TI  - Overexpression of the human DEK oncogene reprograms cellular metabolism and 
      promotes glycolysis.
PG  - e0177952
LID - 10.1371/journal.pone.0177952 [doi]
LID - e0177952
AB  - 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.
FAU - Matrka, Marie C
AU  - Matrka MC
AUID- ORCID: 0000-0002-1885-6582
AD  - Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical 
      Center and University of Cincinnati, Cincinnati, Ohio, United States of America.
FAU - Watanabe, Miki
AU  - Watanabe M
AD  - NMR-Based Metabolomics Core Facility, Division of Pathology and Laboratory 
      Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United 
      States of America.
FAU - Muraleedharan, Ranjithmenon
AU  - Muraleedharan R
AD  - Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical 
      Center and University of Cincinnati, Cincinnati, Ohio, United States of America.
FAU - Lambert, Paul F
AU  - Lambert PF
AD  - McArdle Laboratory for Cancer Research, University of Wisconsin School of 
      Medicine and Public Health, Madison, Wisconsin, United States of America.
FAU - Lane, Andrew N
AU  - Lane AN
AD  - Center for Environmental Systems Biochemistry, Dept. Toxicology and Cancer 
      Biology and Markey Cancer Center, Lexington, Kentucky, United States of America.
FAU - Romick-Rosendale, Lindsey E
AU  - Romick-Rosendale LE
AD  - NMR-Based Metabolomics Core Facility, Division of Pathology and Laboratory 
      Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United 
      States of America.
FAU - Wells, Susanne I
AU  - Wells SI
AD  - Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical 
      Center and University of Cincinnati, Cincinnati, Ohio, United States of America.
LA  - eng
GR  - P30 DK078392/DK/NIDDK NIH HHS/United States
GR  - R01 CA116316/CA/NCI NIH HHS/United States
GR  - U24 DK097215/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20170530
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (DEK protein, human)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Poly-ADP-Ribose Binding Proteins)
SB  - IM
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Chromosomal Proteins, Non-Histone/*genetics
MH  - Flow Cytometry
MH  - Gene Knockdown Techniques
MH  - Glycolysis/*genetics
MH  - Humans
MH  - Keratinocytes/*metabolism
MH  - Metabolomics
MH  - Oncogene Proteins/*genetics
MH  - *Oncogenes
MH  - Poly-ADP-Ribose Binding Proteins
MH  - Proton Magnetic Resonance Spectroscopy
PMC - PMC5448751
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/05/31 06:00
MHDA- 2017/09/22 06:00
PMCR- 2017/05/30
CRDT- 2017/05/31 06:00
PHST- 2017/02/15 00:00 [received]
PHST- 2017/05/05 00:00 [accepted]
PHST- 2017/05/31 06:00 [entrez]
PHST- 2017/05/31 06:00 [pubmed]
PHST- 2017/09/22 06:00 [medline]
PHST- 2017/05/30 00:00 [pmc-release]
AID - PONE-D-17-06031 [pii]
AID - 10.1371/journal.pone.0177952 [doi]
PST - epublish
SO  - PLoS One. 2017 May 30;12(5):e0177952. doi: 10.1371/journal.pone.0177952. 
      eCollection 2017.