Identification of the FoxM1/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma
Menée in vitro et in vivo, cette étude met en évidence le rôle joué par la voie de signalisation FoxM1/Bub1b dans la croissance et la survie des cellules de rhabdomyosarcome
We identified Bub1b as an essential element for the growth and survival of rhabdomyosarcoma (RMS) cells using a bar-coded, tetracycline-inducible shRNA library screen. Knockdown of Bub1b resulted in suppression of tumor growth in vivo, including the regression of established tumors. The mechanism by which this occurs is via post-mitotic endoreduplication checkpoint and mitotic catastrophe. Furthermore, using a chromatin immunoprecipitation (ChIP) assay we found that Bub1b is a direct transcriptional target of Forkhead Box M1 (FoxM1). Suppression of FoxM1 either by shRNA or the inhibitor siomycin A resulted in reduction of Bub1b expression and inhibition of cell growth and survival. These results demonstrate the important role of the Bub1b/FoxM1 pathway in RMS and provide potential therapeutic targets.