Research Project: Oncostatin M proteininin kas dokusu atrofisi üzerine etkilerinin araştırılması
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Contributors
Funders
ID
TB.00346
Authors
Kır, Serkan
Faculty Member
Publications
Oncostatin M signaling drives cancer-associated skeletal muscle wasting
(Cell Press, 2024) Ağca, Samet; Arabacı, Hilal Dilşad; Bilgiç, Şevval Nur; Kashgari, Aynur Erkin; Kır, Serkan; Özen, Sevgi Döndü; Sucuoğlu, Melis; Toledo, Batu; Waraich, Aylin Domaniku; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; Yes; College of Sciences; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
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.
The role of interleukin-6 family cytokines in cancer cachexia
(Wiley, 2024) Ağca, Samet; Kır, Serkan; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; Yes; College of Sciences; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
Cachexia is a wasting syndrome that manifests in more than half of all cancer patients. Cancer-associated cachexia negatively influences the survival of patients and their quality of life. It is characterized by a rapid loss of adipose and skeletal muscle tissues, which is partly mediated by inflammatory cytokines. Here, we explored the crucial roles of interleukin-6 (IL-6) family cytokines, including IL-6, leukemia inhibitory factor, and oncostatin M, in the development of cancer cachexia. These cytokines have been shown to exacerbate cachexia by promoting the wasting of adipose and muscle tissues, activating mechanisms that enhance lipolysis and proteolysis. Overlapping effects of the IL-6 family cytokines depend on janus kinase/signal transducer and activator of transcription 3 signaling. We argue that the blockade of these cytokine pathways individually may fail due to redundancy and future therapeutic approaches should target common downstream elements to yield effective clinical outcomes.
