Browsing by Author "Walter, Glenn A."

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    Blocking muscle wasting via deletion of the muscle-specific E3 ligase MuRF1 impedes pancreatic tumor growth
    (Springer Nature, 2023-05-13) Neyroud, Daria; Laitano, Orlando; Dasgupta, Aneesha; Lopez, Christopher; Schmitt, Rebecca E.; Schneider, Jessica Z.; Hammers, David W.; Sweeney, H. Lee; Walter, Glenn A.; Doles, Jason; Judge, Sarah M.; Judge, Andrew R.; Anatomy, Cell Biology and Physiology, School of Medicine
    Cancer-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.