Neyroud, DariaLaitano, OrlandoDasgupta, AneeshaLopez, ChristopherSchmitt, Rebecca E.Schneider, Jessica Z.Hammers, David W.Sweeney, H. LeeWalter, Glenn A.Doles, JasonJudge, Sarah M.Judge, Andrew R.2023-10-312023-10-312023-05-13Neyroud D, Laitano O, Dasgupta A, et al. Blocking muscle wasting via deletion of the muscle-specific E3 ligase MuRF1 impedes pancreatic tumor growth. Commun Biol. 2023;6(1):519. Published 2023 May 13. doi:10.1038/s42003-023-04902-2https://hdl.handle.net/1805/36789Cancer-induced muscle wasting reduces quality of life, complicates or precludes cancer treatments, and predicts early mortality. Herein, we investigate the requirement of the muscle-specific E3 ubiquitin ligase, MuRF1, for muscle wasting induced by pancreatic cancer. Murine pancreatic cancer (KPC) cells, or saline, were injected into the pancreas of WT and MuRF1-/- mice, and tissues analyzed throughout tumor progression. KPC tumors induces progressive wasting of skeletal muscle and systemic metabolic reprogramming in WT mice, but not MuRF1-/- mice. KPC tumors from MuRF1-/- mice also grow slower, and show an accumulation of metabolites normally depleted by rapidly growing tumors. Mechanistically, MuRF1 is necessary for the KPC-induced increases in cytoskeletal and muscle contractile protein ubiquitination, and the depression of proteins that support protein synthesis. Together, these data demonstrate that MuRF1 is required for KPC-induced skeletal muscle wasting, whose deletion reprograms the systemic and tumor metabolome and delays tumor growth.en-USAttribution 4.0 InternationalPhysiologyCancerMuscular atrophyPancreatic neoplasmsUbiquitin-protein ligasesArticle