Dystrophin glycoprotein complex dysfunction: A regulatory link between muscular dystrophy and cancer cachexia

Swarnali Acharyya, Matthew E.R. Butchbach, Zarife Sahenk, Huating Wang, Motoyasu Saji, Micheal Carathers, Matthew D. Ringel, Richard J.E. Skipworth, Kenneth C.H. Fearon, Michael A. Hollingsworth, Peter Muscarella, Arthur H.M. Burghes, Jill A. Rafael-Fortney, Denis C. Guttridge

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181 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)421-432
Number of pages12
JournalCancer Cell
Volume8
Issue number5
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Acharyya, S., Butchbach, M. E. R., Sahenk, Z., Wang, H., Saji, M., Carathers, M., Ringel, M. D., Skipworth, R. J. E., Fearon, K. C. H., Hollingsworth, M. A., Muscarella, P., Burghes, A. H. M., Rafael-Fortney, J. A., & Guttridge, D. C. (2005). Dystrophin glycoprotein complex dysfunction: A regulatory link between muscular dystrophy and cancer cachexia. Cancer Cell, 8(5), 421-432. https://doi.org/10.1016/j.ccr.2005.10.004