Author/Authors :
Acharyya، نويسنده , , Swarnali and Butchbach، نويسنده , , Matthew E.R. and Sahenk، نويسنده , , Zarife and Wang، نويسنده , , Huating and Saji، نويسنده , , Motoyasu and Carathers، نويسنده , , Micheal and Ringel، نويسنده , , Matthew D. and Skipworth، نويسنده , , Richard J.E. and Fearon، نويسنده , , Kenneth C.H. and Hollingsworth، نويسنده , , Michael A. and Muscarella، نويسنده , , Peter and Burghes، نويسنده , , Arthur H.M. and Rafael-Fortney، نويسنده , , Jill A. and Guttridge، نويسنده , , Denis C.، نويسنده ,
Abstract :
Summary
ia 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.
