Cachexia (亦称肌肉浪费)是癌症晚期导致病人衰弱的一个原因。Acharyya等发现癌症所致Cachexia与dystrophin糖蛋白复合体(DGC)功能丧失相关. 肿瘤的发展导致dystrophin 减少和DGC糖基化失常。Cachexia在dystrophin 缺损小鼠中加剧, 在dystrophin转基因小鼠中则消失. 因此, DGC功能失常可能是癌症患者Cachexia一个根本原因。

Dystrophin glycoprotein complex dysfunction: A regulatory link between muscular dystrophy and cancer cachexia S. Acharyya, M.E.R. Butchbach, Z. Sahenk, H. Wang, M. Saji, M. Carathers, M.D. Ringel, R.J.E. Skipworth, K.C.H. Fearon, M.A. Hollingsworth, P. Muscarella, A.H.M. Burghes, J.A. Rafael-Fortney, and D.C. Guttridge http://www.cancercell.org/cgi/content/abstract/8/5/421 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.