title: Common chromosomal fragile site FRA16D tumor suppressor WWOX gene expression and metabolic reprograming in cells.
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.
authors.affiliation: Discipline of Genetics, School of Molecular and Biomedical Sciences and ARC Special Research Centre for the Molecular Genetics of Development, The University of Adelaide, Adelaide, SA, 5005, Australia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Dayan
authors.forename: Louise V
authors.initials: LV
authors.lastname: O'Keefe
authors.forename: Amanda
authors.initials: A
authors.lastname: Choo
authors.forename: Robert I
authors.initials: RI
authors.lastname: Richards
mesh_terms: D015687:Cell Hypoxia; D043283:Chromosome Fragile Sites; D005690:Galactose / Q000378:metabolism; D006019:Glycolysis; D057809:HEK293 Cells; D006801:Humans; D010085:Oxidative Phosphorylation; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; D005690:Galactose