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Type: Journal article
Title: Common chromosomal fragile site FRA16D tumor suppressor WWOX gene expression and metabolic reprograming in cells
Author: Dayan, S.
O'Keefe, L.
Choo, A.
Richards, R.
Citation: Genes Chromosomes & Cancer, 2013; 52(9):823-831
Publisher: Wiley-Liss
Issue Date: 2013
ISSN: 1045-2257
Statement of
Sonia Dayan, Louise V. O’Keefe, Amanda Choo, and Robert I. Richards
Abstract: The WWOX gene spans the FRA16D common chromosomal fragile site and is able to suppress tumor growth. FRA16D is a frequent site of DNA instability in cancer resulting in reduced levels of WWOX expression. Altered levels of WWOX have been shown to affect metabolism. Whereas metabolic reprograming of cells from oxidative phosphorylation to aerobic glycolysis is a major hallmark of tumors, the relationship between common chromosomal fragile site genes and altered metabolism has been unclear. Here we report that altering metabolism from glycolysis to oxidative phosphorylation causes stable increase in steady-state levels of transcripts of the WWOX gene. Consistent with this, exposure to hypoxic conditions, in which cells rely on glycolysis, causes a downregulation of WWOX mRNA. The function of WWOX is therefore intimately integrated with metabolism, as WWOX not only contributes to the metabolic state of cells, its transcript levels are also linked to intracellular metabolic state.
Keywords: Humans; Reactive Oxygen Species; Oxidoreductases; Galactose; Tumor Suppressor Proteins; Cell Hypoxia; Up-Regulation; Oxidative Phosphorylation; Glycolysis; Chromosome Fragile Sites; HEK293 Cells
Rights: Copyright © 2013 Wiley Periodicals, Inc.
RMID: 0020130846
DOI: 10.1002/gcc.22078
Appears in Collections:Genetics publications

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