Dystrophin glycoprotein complex dysfunction: A regulatory link between muscular dystrophy and cancer cachexia
Dystrophin glycoprotein complex dysfunction: A regulatory link between muscular dystrophy and cancer cachexia
复制标题
DOI：
10.1016/j.ccr.2005.10.004
复制
发表时间：
2005-11-01
期刊：
影响因子：
50.3
通讯作者：
Guttridge, DC
中科院分区：
文献类型：
--
作者：
Acharyya, S;Butchbach, MER;Guttridge, DC
恶病质导致近三分之一的癌症死亡，但这种综合征中骨骼肌萎缩的机制仍然不清楚。我们报告肿瘤诱导的肌营养不良相关肌营养不良蛋白糖蛋白复合物（DGC）的改变是恶病质的一个关键早期事件。来自荷瘤小鼠的肌肉表现出膜异常，伴随着抗肌萎缩蛋白水平降低和DGC蛋白糖基化增加。消瘦在缺乏DGC的肿瘤mdx小鼠中加重，但在阻断肌肉E3泛素连接酶诱导的抗肌萎缩蛋白转基因小鼠中幸免。此外，DGC失调与胃肠道癌症患者的恶病质呈正相关。基于这些结果，我们提出，类似于肌营养不良症，DGC功能障碍在癌症引起的消瘦中起着关键作用。
Cachexia contributes to nearly a third of all cancer deaths, yet the mechanisms underlying skeletal muscle wasting in this syndrome remain poorly defined. We report that tumor-induced alterations in the muscular dystrophy-associated dystrophin glycoprotein complex (DGC) represent a key early event in cachexia. Muscles from tumor-bearing mice exhibited membrane abnormalities accompanied by reduced levels of dystrophin and increased glycosylation on DGC proteins. Wasting was accentuated in tumor mdx mice lacking a DGC but spared in dystrophin transgenic mice that blocked induction of muscle E3 ubiquitin ligases. Furthermore, DGC deregulation correlated positively with cachexia in patients with gastrointestinal cancers. Based on these results, we propose that, similar to muscular dystrophy, DGC dysfunction plays a critical role in cancer-induced wasting.