The TWEAK/Fn14 signaling mediates skeletal muscle wasting during cancer cachexia.

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 tumo

SUBMITTER: Tomaz da Silva M 

PROVIDER: S-EPMC12205822 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature