| First Author | Domaniku-Waraich A | Year | 2024 |
| Journal | Cell Rep Med | Volume | 5 |
| Issue | 4 | Pages | 101498 |
| PubMed ID | 38569555 | Mgi Jnum | J:375182 |
| Mgi Id | MGI:8240245 | Doi | 10.1016/j.xcrm.2024.101498 |
| Citation | Domaniku-Waraich A, et al. (2024) Oncostatin M signaling drives cancer-associated skeletal muscle wasting. Cell Rep Med 5(4):101498 |
| abstractText | Progressive weakness and muscle loss are associated with multiple chronic conditions, including muscular dystrophy and cancer. Cancer-associated cachexia, characterized by dramatic weight loss and fatigue, leads to reduced quality of life and poor survival. Inflammatory cytokines have been implicated in muscle atrophy; however, available anticytokine therapies failed to prevent muscle wasting in cancer patients. Here, we show that oncostatin M (OSM) is a potent inducer of muscle atrophy. OSM triggers cellular atrophy in primary myotubes using the JAK/STAT3 pathway. Identification of OSM targets by RNA sequencing reveals the induction of various muscle atrophy-related genes, including Atrogin1. OSM overexpression in mice causes muscle wasting, whereas muscle-specific deletion of the OSM receptor (OSMR) and the neutralization of circulating OSM preserves muscle mass and function in tumor-bearing mice. Our results indicate that activated OSM/OSMR signaling drives muscle atrophy, and the therapeutic targeting of this pathway may be useful in preventing muscle wasting. |
