Results:
Here, we show that an enhanced interaction between activated STAT3 and
HSP90, which were observed in the skeletal muscle of cancer cachexia
patients, is a crucial event for the development of cachectic muscle
wasting. Administration of HSP90 inhibitors 17DMAG and PU-H71 alleviated
the muscle wasting in C26 and LLC tumor-bearing cachectic mice models or
the myotube atrophy of C2C12 cells induced by C26 conditional medium.
Prolonged STAT3 activation transactivated FOXO1 by binding directly to
its promoter and triggered the muscle wasting in a FOXO1-dependent
manner in muscle cells.