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

ABSTRACT: Cancer-induced muscle wasting reduces quality of life, complicates or precludes cancer treatments, and predicts early mortality. Herein, we investigated 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 induced progressive wasting of skeletal muscle and systemic metabolic reprogramming in WT mice, but not MuRF1-/- mice. KPC tumors from MuRF1-/- mice also grew slower, and showed an accumulation of metabolites normally depleted by rapidly growing tumors. Mechanistically, MuRF1 was 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skeletal Muscle

DISEASE(S): Pancreatic Cancer

SUBMITTER: Daria Neyroud  

LAB HEAD: Andrew R Judge

PROVIDER: PXD039158 | Pride | 2023-05-15

REPOSITORIES: Pride