Blocking muscle wasting via deletion of the muscle-specific E3 ligase MuRF1 impedes pancreatic tumor growth


Cancer-induced muscle wasting significantly impacts quality of life, hinders cancer treatments, and predicts early mortality. This study explores the role of the muscle-specific E3 ubiquitin ligase, MuRF1, in pancreatic cancer-induced muscle wasting. Using murine pancreatic cancer cells, the researchers found that tumors induce progressive muscle wasting and metabolic changes in wild-type (WT) mice but not in MuRF1-deficient mice. Tumors in MuRF1-deficient mice also exhibit slower growth and an accumulation of metabolites normally depleted in rapidly growing tumors. Mechanistically, MuRF1 is crucial for the increased ubiquitination of cytoskeletal and muscle contractile proteins induced by pancreatic cancer, as well as the suppression of proteins supporting protein synthesis. These results reveal that MuRF1 is essential for pancreatic cancer-induced muscle wasting, and its deletion reprograms the systemic and tumor metabolome while delaying tumor growth.