The canonical ER stress IRE1α/XBP1 pathway mediates skeletal muscle wasting during pancreatic cancer cachexia.

ABSTRACT: Cancer-driven cachexia is a deleterious syndrome which involves progressive loss of skeletal muscle mass with or without fat loss, fatigue, and weakness that cannot be reversed by nutritional intake. Recent studies have shown deregulation of endoplasmic reticulum (ER)-induced unfolded protein response (UPR) pathways in skeletal muscle in various catabolic conditions, including cancer growth. However, the role of individual arms of the UPR in the regulation of muscle mass remains poorly understood. Here, we demonstrate that the IRE1α/XBP1 arm of the UPR stimulates the activation of ubiquitin-proteasome system, autophagy, JAK-STAT3 signaling, and fatty acid metabolism in skeletal muscle of the KPC mouse model of pancreatic cancer cachexia. Furthermore, our results show that IRE1α/XBP1 pathwa

SUBMITTER: Joshi AS 

PROVIDER: S-EPMC12247886 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature