FoxP1 is a transcriptional repressor associated with cancer cachexia that induces skeletal muscle wasting and weakness

Background Skeletal muscle wasting is a devastating consequence of cancer that affects up to 80% of cancer patients and associates with reduced survival. Herein, we investigated the biological significance of Forkhead box P1 (FoxP1), a transcriptional repressor that we demonstrate is up‐regulated in skeletal muscle in multiple models of cancer cachexia and in cachectic cancer patients. Methods Inducible, skeletal muscle‐specific FoxP1 over‐expressing (FoxP1iSkmTg/Tg) mice were generated through crossing conditional Foxp1a transgenic mice with HSA‐MCM mice that express tamoxifen‐inducible Cre recombinase under control of the skeletal muscle actin promoter. To determine the requirement of FoxP1 for cancer‐induced skeletal muscle wasting, FoxP1‐shRNA was packaged and targeted to muscles using AAV9 delivery prior to inoculation of mice with Colon‐26 Adenocarcinoma (C26) cells. Results Up‐regulation of FoxP1 in adult skeletal muscle was sufficient to induce features of cachexia, including 15% reduction in body mass (P