Drosophila orthologue of WWOX, the chromosomal fragile site FRA16D tumour suppressor gene, functions in aerobic metabolism and regulates reactive oxygen species.
Drosophila orthologue of WWOX, the chromosomal fragile site FRA16D tumour suppressor gene, functions in aerobic metabolism and regulates reactive oxygen species.
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DOI：
10.1093/hmg/ddq495
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发表时间：
2011-02-01
影响因子：
3.5
通讯作者：
Richards RI
中科院分区：
文献类型：
--
作者：
O'Keefe LV;Colella A;Dayan S;Chen Q;Choo A;Jacob R;Price G;Venter D;Richards RI
常见的染色体脆性位点FRA 3B和FRA 16 D是癌症中DNA不稳定性的常见位点，但它们对癌细胞生物学的贡献尚不清楚。跨越这些位点的基因（分别为FHIT和WWOX）通常在癌细胞中受到干扰（增加或减少），并且两者都能够抑制肿瘤生长。虽然WWOX具有一些肿瘤抑制特性，但其对癌症的正常作用和功能贡献尚未完全确定。我们发现，一个显着比例的果蝇Wwox相互作用蛋白质组学和微阵列分析确定有氧代谢的作用。Wwox与CG 6439/异柠檬酸脱氢酶（Idh）或铜锌超氧化物歧化酶（SOD）之间的功能关系被证实的遗传相互作用。此外，Wwox水平的改变导致内源性活性氧水平的改变。WWOX（如FHIT）有助于涉及有氧代谢和氧化应激的途径，为WWOX的“非经典肿瘤抑制剂”行为提供了解释。因此，脆弱位点和跨越它们的基因是对氧化应激的保护性反应机制的一部分，并且可能是癌细胞中有氧糖酵解（瓦尔堡效应）中所见差异的贡献者。
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.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1016/j.bbrc.2010.06.125
发表时间：
2010-07-30
影响因子：
3.1
作者：
Lopez, Giselle Y.;Reitman, Zachary J.;Yan, Hai
通讯作者：
Yan, Hai
影响因子：
3.4
作者：
Kölker, S;Pawlak, V;Köhr, G
通讯作者：
Köhr, G
影响因子：
4.8
作者：
Chang, NS;Pratt, N;Zevotek, N
通讯作者：
Zevotek, N
影响因子：
3.7
作者：
Ludes-Meyers, John H.;Kil, Hyunsuk;Aldaz, C. Marcelo
通讯作者：
Aldaz, C. Marcelo