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Type: Journal article
Title: Tumor suppressor WWOX contributes to the elimination of tumorigenic cells in drosophila melanogaster
Author: O'Keefe, L.
Lee, C.
Choo, A.
Richards, R.
Citation: PLoS One, 2015; 10(8):e0136356-1-e0136356-19
Publisher: Public Library of Science
Issue Date: 2015
ISSN: 1932-6203
Statement of
Louise V. O, Keefe, Cheng Shoou Lee, Amanda Choo, Robert I. Richards
Abstract: WWOX is a >1Mb gene spanning FRA16D Common Chromosomal Fragile Site, a region of DNA instability in cancer. Consequently, altered WWOX levels have been observed in a wide variety of cancers. In vitro studies have identified a large number and variety of potential roles for WWOX. Although its normal role in vivo and functional contribution to cancer have not been fully defined, WWOX does have an integral role in metabolism and can suppress tumor growth. Using Drosophila melanogaster as an in vivo model system, we find that WWOX is a modulator of TNFα/Egr-mediated cell death. We found that altered levels of WWOX can modify phenotypes generated by low level ectopic expression of TNFα/Egr and this corresponds to altered levels of Caspase 3 activity. These results demonstrate an in vivo role for WWOX in promoting cell death. This form of cell death is accompanied by an increase in levels of reactive oxygen species, the regulation of which we have previously shown can also be modified by altered WWOX activity. We now hypothesise that, through regulation of reactive oxygen species, WWOX constitutes a link between alterations in cellular metabolism observed in cancer cells and their ability to evade normal cell death pathways. We have further shown that WWOX activity is required for the efficient removal of tumorigenic cells from a developing epithelial tissue. Together these results provide a molecular basis for the tumor suppressor functions of WWOX and the better prognosis observed in cancer patients with higher levels of WWOX activity. Understanding the conserved cellular pathways to which WWOX contributes provides novel possibilities for the development of therapeutic approaches to restore WWOX function in cancer.
Keywords: Animals; Humans; Drosophila melanogaster; Neoplasms; Cell Transformation, Neoplastic; Disease Models, Animal; Tumor Necrosis Factor-alpha; Drosophila Proteins; Tumor Suppressor Proteins; Cell Death; Gene Expression Regulation, Neoplastic; Chromosome Fragile Sites; Caspase 3
Rights: © 2015 O’Keefe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
RMID: 0030034344
DOI: 10.1371/journal.pone.0136356
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Appears in Collections:Genetics publications

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