Necdin is expressed in cachectic skeletal muscle to protect fibers from tumor-induced wasting

Clara Sciorati, Thierry Touvier, Roberta Buono, Patrizia Pessina, Stephanie François, Cristiana Perrotta, Raffaella Meneveri, Emilio Clementi, Silvia Brunelli

Research output: Contribution to journalArticlepeer-review

Abstract

Skeletal muscles of subjects with advanced cancer undergo progressive wasting, referred to as cachexia. Cachexia is an important area for medical research because strategies proposed until now have yielded little benefit. We have recently identified necdin as a key player in fetal and postnatal physiological myogenesis and in muscle regeneration. Here we show that necdin is selectively expressed in muscles of cachetic mice and prove that its expression is causally linked to a protective response of the tissue against tumor-induced wasting, inhibition of myogenic differentiation and fiber regeneration. Necdin carries out this role mainly via interference with TNFα signaling at various levels, including regulation of expression of TNFR1 and p53, and regulation of the activity of caspase 3 and caspase 9. These data suggest that inhibition of muscle wasting using necdin is a feasible approach to treat cachexia in neoplastic patients.

Original languageEnglish
Pages (from-to)1119-1125
Number of pages7
JournalJournal of Cell Science
Volume122
Issue number8
DOIs
Publication statusPublished - Apr 15 2009

Keywords

  • Cachexia
  • Muscle regeneration
  • Necdin
  • TNFα

ASJC Scopus subject areas

  • Cell Biology

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