Common chromosomal fragile site FRA16D tumor suppressor WWOX gene expression and metabolic reprograming in cells. Issue 9 (13th June 2013)

• Record Type: Journal Article
• Authors: Dayan, Sonia; O'Keefe, Louise V.; Choo, Amanda; Richards, Robert I.
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 9(2013:Sep.)
• Page Start: 823
• Page End: 831
• Publication Date: 2013-06-13
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22078
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The <italic>WWOX</italic> gene spans the <italic>FRA16D</italic> common chromosomal fragile site and is able to suppress tumor growth. <italic>FRA16D</italic> is a frequent site of DNA instability in cancer resulting in reduced levels of <italic>WWOX</italic> expression. Altered levels of <italic>WWOX</italic> 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 <italic>WWOX</italic> gene. Consistent with this, exposure to hypoxic conditions, in which cells rely on glycolysis, causes a downregulation of <italic>WWOX</italic> mRNA. The function of <italic>WWOX</italic> is therefore intimately integrated with metabolism, as <italic>WWOX</italic> not only contributes to the metabolic state of cells, its transcript levels are also linked to intracellular metabolic state. © 2013 Wiley Periodicals, Inc.</p> </abstract>