Aqeilan Rami I, Abu-Remaileh Muhannad, Abu-Odeh Mohammad
The Lautenberg Center for Immunology and Cancer Research, IMRIC, Faculty of Medicine, Hebrew University of Jerusalem, 91220, Jerusalem, Israel,
Cell Mol Life Sci. 2014 Dec;71(23):4589-99. doi: 10.1007/s00018-014-1724-y. Epub 2014 Sep 23.
The fragile WWOX gene, encompassing the chromosomal fragile site FRA16D, is frequently altered in human cancers. While vulnerable to DNA damage itself, recent evidence has shown that the WWOX protein is essential for proper DNA damage response (DDR). Furthermore, the gene product, WWOX, has been associated with multiple protein networks, highlighting its critical functions in normal cell homeostasis. Targeted deletion of Wwox in murine models suggests its in vivo requirement for proper growth, metabolism, and survival. Recent molecular and biochemical analyses of WWOX functions highlighted its role in modulating aerobic glycolysis and genomic stability. Cumulatively, we propose that the gene product of FRA16D, WWOX, is a functionally essential protein that is required for cell homeostasis and that its deletion has important consequences that contribute to the neoplastic process. This review discusses the essential role of WWOX in tumor suppression and genomic stability and how its alteration contributes to cancer transformation.
包含染色体脆性位点FRA16D的脆弱WWOX基因在人类癌症中经常发生改变。尽管其自身易受DNA损伤，但最近的证据表明，WWOX蛋白对于适当的DNA损伤反应（DDR）至关重要。此外，基因产物WWOX与多个蛋白质网络相关联，突出了其在正常细胞稳态中的关键功能。在小鼠模型中靶向缺失Wwox表明其在体内对于正常生长、代谢和存活的必要性。最近对WWOX功能的分子和生化分析突出了其在调节有氧糖酵解和基因组稳定性中的作用。总体而言，我们提出FRA16D的基因产物WWOX是一种功能上必不可少的蛋白质，是细胞稳态所必需的，其缺失具有导致肿瘤形成过程的重要后果。本综述讨论了WWOX在肿瘤抑制和基因组稳定性中的重要作用，以及其改变如何促成癌症转化。
