TY - JOUR
T1 - Dystrophin glycoprotein complex dysfunction
T2 - a regulatory link between muscular dystrophy and cancer cachexia
AU - Acharyya, Swarnali
AU - Butchbach, Matthew E R
AU - Sahenk, Zarife
AU - Wang, Huating
AU - Saji, Motoyasu
AU - Carathers, Micheal
AU - Ringel, Matthew D
AU - Skipworth, Richard J E
AU - Fearon, Kenneth C H
AU - Hollingsworth, Michael A
AU - Muscarella, Peter
AU - Burghes, Arthur H M
AU - Rafael-Fortney, Jill A
AU - Guttridge, Denis C
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
U2 - 10.1016/j.ccr.2005.10.004
DO - 10.1016/j.ccr.2005.10.004
M3 - Article
C2 - 16286249
SN - 1535-6108
VL - 8
SP - 421
EP - 432
JO - Cancer Cell
JF - Cancer Cell
IS - 5
ER -