P38β MAPK mediates ULK1-dependent induction of autophagy in skeletal muscle of tumor-bearing mice.

ABSTRACT: Muscle wasting is the key manifestation of cancer-associated cachexia, a lethal metabolic disorder seen in over 50% of cancer patients. Autophagy is activated in cachectic muscle of cancer hosts along with the ubiquitin-proteasome pathway (UPP), contributing to accelerated protein degradation and muscle wasting. However, established signaling mechanism that activates autophagy in response to fasting or denervation does not seem to mediate cancer-provoked autophagy in skeletal myocytes. Here, we show that p38β MAPK mediates autophagy activation in cachectic muscle of tumor-bearing mice via novel mechanisms. Complementary genetic and pharmacological manipulations reveal that activation of p38β MAPK, but not p38α MAPK, is necessary and sufficient for Lewis lung carcinoma (LLC)-induced autopha

SUBMITTER: Liu Z 

PROVIDER: S-EPMC6551802 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature