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

J Cell Sci. 2009 Apr 15;122(Pt 8):1119-25. doi: 10.1242/jcs.041665.

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 TNFalpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Animals
  • Cachexia / etiology
  • Cachexia / metabolism
  • Cachexia / pathology
  • Cachexia / prevention & control*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Differentiation
  • Cell Line, Tumor
  • Colonic Neoplasms / complications
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Regeneration
  • Signal Transduction
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Receptors, Tumor Necrosis Factor, Type I
  • Tnfrsf1a protein, mouse
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • necdin
  • Casp3 protein, mouse
  • Casp9 protein, mouse
  • Caspase 3
  • Caspase 9