Suppression of the Oncogenic Transcription Factor FOXM1 by Proteasome Inhibitors

摘要: The oncogenic transcription factor FOXM1 is one of the key regulators tumorigenesis. We found that upregulates its own and protein stability depends on interaction with chaperone nucleophosmin. also determined negatively regulated by tumor suppressor p53. identified thiazole antibiotics Siomycin A thiostrepton as inhibitors transcriptional activity expression via proteasome inhibition. In addition, we all tested target FOXM1. showed synergy between bortezomib in different human cancer cell lines vivo. generated isogenic origin wild-type p53 or knockdown demonstrated induce p53-independent apoptosis these cells. Using RNA-interference to inhibit suppression sensitized cells induced DNA-damaging agents oxidative stress. encapsulated into micelle-nanoparticles after injection detected accumulation nanoparticles tumors livers treated mice. This treatment led inhibition xenograft growth nude Our data indicate targeting increases inhibits growth.