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Article Dans Une Revue Cancer Research Année : 2014

Myostatin Gene Inactivation Prevents Skeletal Muscle Wasting in Cancer

Yann S. Gallot
Barbara Vernus
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Didier Remond
Dominique Dardevet
Anne Bonnieu

Résumé

Cachexia is a muscle-wasting syndrome that contributes significantly to morbidity and mortality of many patients with advanced cancers. However, little is understood about how the severe loss of skeletal muscle characterizing this condition occurs. In the current study, we tested the hypothesis that the muscle protein myostatin is involved in mediating the pathogenesis of cachexia-induced muscle wasting in tumor-bearing mice. Myostatin gene inactivation prevented the severe loss of skeletal muscle mass induced in mice engrafted with Lewis lung carcinoma (LLC) cells or in Apc(Min/+) mice, an established model of colorectal cancer and cachexia. Mechanistically, myostatin loss attenuated the activation of muscle fiber proteolytic pathways by inhibiting the expression of atrophy-related genes, MuRF1 and MAFbx/Atrogin-1, along with autophagy-related genes. Notably, myostatin loss also impeded the growth of LLC tumors, the number and the size of intestinal polyps in Apc(Min/+) mice, thus strongly increasing survival in both models. Gene expression analysis in the LLC model showed this phenotype to be associated with reduced expression of genes involved in tumor metabolism, activin signaling, and apoptosis. Taken together, our results reveal an essential role for myostatin in the pathogenesis of cancer cachexia and link this condition to tumor growth, with implications for furthering understanding of cancer as a systemic disease. (C)2014 AACR.

Dates et versions

hal-01837578 , version 1 (12-07-2018)

Identifiants

Citer

Yann S. Gallot, Anne-Cécile Durieux, Josiane Castells, Marine M. Desgeorges, Barbara Vernus, et al.. Myostatin Gene Inactivation Prevents Skeletal Muscle Wasting in Cancer. Cancer Research, 2014, 74 (24), pp.7344-7356. ⟨10.1158/0008-5472.can-14-0057⟩. ⟨hal-01837578⟩
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