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https://hdl.handle.net/2440/65788
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Type: | Journal article |
Title: | Drosophila orthologue of WWOX, the chromosomal fragile site FRA16D tumour suppressor gene, functions in aerobic metabolism and regulates reactive oxygen species |
Author: | O'Keefe, L. Colella, A. De Barros Lopes, S. Chen, Q. Choo, A. Jacob, R. Price, G. Venter, D. Richards, R. |
Citation: | Human Molecular Genetics, 2011; 20(3):497-509 |
Publisher: | Oxford Univ Press |
Issue Date: | 2011 |
ISSN: | 0964-6906 1460-2083 |
Statement of Responsibility: | Louise V. O'Keefe, Alex Colella, Sonia Dayan, Qingwen Chen, Amanda Choo, Reuben Jacob, Gareth Price, Deon Venter and Robert I. Richards |
Abstract: | Common chromosomal fragile sites FRA3B and FRA16D are frequent sites of DNA instability in cancer, but their contribution to cancer cell biology is not yet understood. Genes that span these sites (FHIT and WWOX, respectively) are often perturbed (either increased or decreased) in cancer cells and both are able to suppress tumour growth. While WWOX has some tumour suppressor characteristics, its normal role and functional contribution to cancer has not been fully determined. We find that a significant proportion of Drosophila Wwox interactors identified by proteomics and microarray analyses have roles in aerobic metabolism. Functional relationships between Wwox and either CG6439/isocitrate dehydrogenase (Idh) or Cu–Zn superoxide dismutase (Sod) were confirmed by genetic interactions. In addition, altered levels of Wwox resulted in altered levels of endogenous reactive oxygen species. Wwox (like FHIT) contributes to pathways involving aerobic metabolism and oxidative stress, providing an explanation for the ‘non-classical tumour suppressor’ behaviour of WWOX. Fragile sites, and the genes that span them, are therefore part of a protective response mechanism to oxidative stress and likely contributors to the differences seen in aerobic glycolysis (Warburg effect) in cancer cells. |
Keywords: | Cell Line, Tumor Animals Humans Drosophila Reactive Oxygen Species Oxidoreductases Isocitrate Dehydrogenase Superoxide Dismutase Drosophila Proteins Tumor Suppressor Proteins Microarray Analysis Polymerase Chain Reaction Proteomics Cell Respiration Gene Expression Aerobiosis Base Sequence Glycolysis Oxidative Stress Genes, Tumor Suppressor Chromosome Fragile Sites Mass Spectrometry Metabolic Networks and Pathways WW Domain-Containing Oxidoreductase |
Rights: | Copyright Authors. Copyright © 2011 Oxford University Press |
DOI: | 10.1093/hmg/ddq495 |
Published version: | http://dx.doi.org/10.1093/hmg/ddq495 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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