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

Research output: Contribution to journalArticle

175 Citations (Scopus)

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 2005
Externally publishedYes

Fingerprint

Dystrophin
Cachexia
Muscular Dystrophies
Glycoproteins
Neoplasms
Inbred mdx Mouse
Wasting Syndrome
Muscles
Gastrointestinal Neoplasms
Ubiquitin-Protein Ligases
Glycosylation
Transgenic Mice
Skeletal Muscle
Membranes

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Acharyya, S., Butchbach, M. E. R., Sahenk, Z., Wang, H., Saji, M., Carathers, M., ... 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

Dystrophin glycoprotein complex dysfunction : A regulatory link between muscular dystrophy and cancer cachexia. / Acharyya, Swarnali; Butchbach, Matthew E R; Sahenk, Zarife; Wang, Huating; Saji, Motoyasu; Carathers, Micheal; Ringel, Matthew D.; Skipworth, Richard J E; Fearon, Kenneth C H; Hollingsworth, Michael A.; Muscarella, Peter; Burghes, Arthur H M; Rafael-Fortney, Jill A.; Guttridge, Denis C.

In: Cancer Cell, Vol. 8, No. 5, 11.2005, p. 421-432.

Research output: Contribution to journalArticle

Acharyya, S, Butchbach, MER, Sahenk, Z, Wang, H, Saji, M, Carathers, M, Ringel, MD, Skipworth, RJE, Fearon, KCH, Hollingsworth, MA, Muscarella, P, Burghes, AHM, Rafael-Fortney, JA & Guttridge, DC 2005, 'Dystrophin glycoprotein complex dysfunction: A regulatory link between muscular dystrophy and cancer cachexia', Cancer Cell, vol. 8, no. 5, pp. 421-432. https://doi.org/10.1016/j.ccr.2005.10.004
Acharyya, Swarnali ; Butchbach, Matthew E R ; Sahenk, Zarife ; Wang, Huating ; Saji, Motoyasu ; Carathers, Micheal ; Ringel, Matthew D. ; Skipworth, Richard J E ; Fearon, Kenneth C H ; Hollingsworth, Michael A. ; Muscarella, Peter ; Burghes, Arthur H M ; Rafael-Fortney, Jill A. ; Guttridge, Denis C. / Dystrophin glycoprotein complex dysfunction : A regulatory link between muscular dystrophy and cancer cachexia. In: Cancer Cell. 2005 ; Vol. 8, No. 5. pp. 421-432.
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