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First published online April 1, 2009
doi: 10.1242/10.1242/jcs.041665

Journal of Cell Science 122, 1119-1125 (2009)
Published by The Company of Biologists 2009
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Research Article

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

Clara Sciorati1, Thierry Touvier1, Roberta Buono1, Patrizia Pessina2, Stephanie François2, Cristiana Perrotta1, Raffaella Meneveri2, Emilio Clementi3,4,* and Silvia Brunelli1,2,*

1 Division of Regenerative Medicine, San Raffaele Scientific Institute, 20132 Milan, Italy
2 Department of Experimental Medicine, University of Milano-Bicocca, 20052 Monza, Italy
3 Department of Preclinical Sciences, LITA-Vialba, University of Milano, 20157 Milan, Italy
4 E. Medea Scientific Institute, 23842 Bosisio Parini, Italy

* Authors for correspondence (e-mails: brunelli.silvia{at}hsr.it; emilio.clementi{at}unimi.it)

Accepted 27 December 2008

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 TNF{alpha} 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.

Key words: Necdin, Cachexia, Muscle regeneration, TNF{alpha}


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© The Company of Biologists Ltd 2009