Faculty, Staff and Student Publications
Language
English
Publication Date
5-30-2025
Journal
iScience
DOI
10.1016/j.isci.2025.112714
PMID
40585358
PMCID
PMC12205822
PubMedCentral® Posted Date
5-30-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Cancer cachexia is a multifactorial syndrome characterized by progressive skeletal muscle wasting. The TWEAK-Fn14 system regulates muscle mass in diverse conditions. However, its role in the regulation of muscle mass during cancer cachexia remains less understood. Here, we demonstrate that the levels of Fn14 are induced in skeletal muscle of multiple mouse models of cancer cachexia. Muscle-specific deletion of Fn14 reduces myofiber atrophy in mouse models of pancreatic and lung cancer cachexia. Silencing of Fn14 in KPC pancreatic cancer cells prior to their implantation in mice attenuates tumor growth without affecting myofiber size. Muscle-specific deletion of Fn14 reduces the gene expression of various components of the PERK and IRE1α arms of the unfolded protein response during KPC tumor growth. The inhibition of PERK improves protein synthesis and average myotube diameter in TWEAK-treated cultures. Altogether, our study suggests that the inhibition of TWEAK/Fn14 signaling can attenuate tumor growth and muscle wasting during cancer cachexia.
Keywords
Molecular biology, Cell biology, Cancer
Published Open-Access
yes
Recommended Citation
Tomaz da Silva, Meiricris; Roy, Anirban; Vuong, Anh Tuan; et al., "The Tweak/Fn14 Signaling Mediates Skeletal Muscle Wasting During Cancer Cachexia" (2025). Faculty, Staff and Student Publications. 6317.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6317
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons