Tumor suppressor WWOX moderates the mitochondrial respiratory complex. Issue 12 (22nd September 2015)

• Record Type: Journal Article
• Authors: Choo, Amanda; O'Keefe, Louise V.; Lee, Cheng Shoou; Gregory, Stephen L.; Shaukat, Zeeshan; Colella, Alexander; Lee, Kristie; Denton, Donna; Richards, Robert I.
• Is Part Of: Genes, chromosomes & cancer. Volume 54:Issue 12(2015:Dec.)
• Page Start: 745
• Page End: 761
• Publication Date: 2015-09-22
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22286
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Fragile site <italic>FRA16D</italic> exhibits DNA instability in cancer, resulting in diminished levels of protein from the <italic>WWOX</italic> gene that spans it. WWOX suppresses tumor growth by an undefined mechanism. WWOX participates in pathways involving aerobic metabolism and reactive oxygen species. WWOX comprises two WW domains as well as a short‐chain dehydrogenase/reductase enzyme. Herein is described an <italic>in vivo</italic> genetic analysis in <italic>Drosophila melanogaster</italic> to identify functional interactions between WWOX and metabolic pathways. Altered WWOX levels modulate variable cellular outgrowths caused by genetic deficiencies of components of the mitochondrial respiratory complexes. This modulation requires the enzyme active site of WWOX, and the defective respiratory complex‐induced cellular outgrowths are mediated by reactive oxygen species, dependent upon the Akt pathway and sensitive to levels of autophagy and hypoxia‐inducible factor. WWOX is known to contribute to homeostasis by regulating the balance between oxidative phosphorylation and glycolysis. Reduction of WWOX levels results in diminished ability to respond to metabolic perturbation of normal cell growth. Thus, the ability of WWOX to facilitate escape from mitochondrial damage‐induced glycolysis (Warburg effect) is, therefore, a plausible mechanism for its tumor suppressor activity. © 2015 Wiley Periodicals, Inc.</p> </abstract>