title: Dystrophin glycoprotein complex dysfunction: a regulatory link between muscular dystrophy and cancer cachexia.
abstract: 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.
authors.affiliation: Human Cancer Genetics Program, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Swarnali
authors.initials: S
authors.lastname: Acharyya
authors.forename: Matthew E R
authors.initials: ME
authors.lastname: Butchbach
authors.forename: Zarife
authors.initials: Z
authors.lastname: Sahenk
authors.forename: Huating
authors.initials: H
authors.lastname: Wang
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Saji
authors.forename: Micheal
authors.initials: M
authors.lastname: Carathers
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Ringel
authors.forename: Richard J E
authors.initials: RJ
authors.lastname: Skipworth
authors.forename: Kenneth C H
authors.initials: KC
authors.lastname: Fearon
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hollingsworth
authors.forename: Peter
authors.initials: P
authors.lastname: Muscarella
authors.forename: Arthur H M
authors.initials: AH
authors.lastname: Burghes
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rafael-Fortney
authors.forename: Denis C
authors.initials: DC
authors.lastname: Guttridge
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002100:Cachexia / Q000150:complications / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism / Q000502:physiology*; D049029:Dystrophin-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D005260:Female; D018703:Founder Effect; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D006023:Glycoproteins; D044767:Ubiquitin-Protein Ligases