Muscular dystrophies share pathogenetic mechanisms with muscle sarcomas

Trends Mol Med. 2013 Sep;19(9):546-54. doi: 10.1016/j.molmed.2013.07.001. Epub 2013 Jul 23.

Abstract

Several lines of recent evidence have opened a new debate on the mechanisms underlying the genesis of rhabdomyosarcoma, a pediatric soft tissue tumor with a widespread expression of muscle-specific markers. In particular, it is increasingly evident that the loss of skeletal muscle integrity observed in some mouse models of muscular dystrophy can favor rhabdomyosarcoma formation. This is especially true in old age. Here, we review these experimental findings and focus on the main molecular and cellular events that can dictate the tumorigenic process in dystrophic muscle, such as the loss of structural or regulatory proteins with tumor suppressor activity, the impaired DNA damage response due to oxidative stress, the chronic inflammation and the conflicting signals arising within the degenerated muscle niche.

Keywords: aging; inflammation; muscle niche; muscular dystrophy; oxidative stress; rhabdomyosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Child
  • DNA Damage / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophies / etiology
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophies / physiopathology
  • Oxidative Stress*
  • Rhabdomyosarcoma / etiology
  • Rhabdomyosarcoma / genetics*
  • Rhabdomyosarcoma / physiopathology