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

Autor: Neyroud D; Department of Physical Therapy, University of Florida, Gainesville, FL, USA.; Myology Institute, University of Florida, Gainesville, FL, USA.; Institute of Sports Sciences, University of Lausanne, Lausanne, Switzerland., Laitano O; Myology Institute, University of Florida, Gainesville, FL, USA.; Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, USA., Dasgupta A; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA., Lopez C; Department of Physical Therapy, University of Florida, Gainesville, FL, USA.; Myology Institute, University of Florida, Gainesville, FL, USA., Schmitt RE; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA., Schneider JZ; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA., Hammers DW; Myology Institute, University of Florida, Gainesville, FL, USA.; Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA., Sweeney HL; Myology Institute, University of Florida, Gainesville, FL, USA.; Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA., Walter GA; Myology Institute, University of Florida, Gainesville, FL, USA.; Department of Physiology and Aging, University of Florida, Gainesville, FL, USA., Doles J; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA., Judge SM; Department of Physical Therapy, University of Florida, Gainesville, FL, USA.; Myology Institute, University of Florida, Gainesville, FL, USA., Judge AR; Department of Physical Therapy, University of Florida, Gainesville, FL, USA. arjudge@phhp.ufl.edu.; Myology Institute, University of Florida, Gainesville, FL, USA. arjudge@phhp.ufl.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 May 13; Vol. 6 (1), pp. 519. Date of Electronic Publication: 2023 May 13.
DOI: 10.1038/s42003-023-04902-2
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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