AI Article Synopsis
- Researchers found that Bub1b is crucial for the growth and survival of rhabdomyosarcoma (RMS) cells through a specific genetic screening method.
- Reducing Bub1b levels led to decreased tumor growth and even regression of existing tumors, operating through a mechanism involving mitotic failure and an important cell division checkpoint.
- Additionally, they discovered that Bub1b is regulated by Forkhead Box M1 (FoxM1), and targeting FoxM1 also lowered Bub1b levels, suggesting a potential therapeutic strategy for treating RMS.
Article Abstract
We identified Bub1b as an essential element for the growth and survival of rhabdomyosarcoma (RMS) cells using a bar-coded, tetracycline-inducible short hairpin RNA (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 postmitotic endoreduplication checkpoint and mitotic catastrophe. Furthermore, using a chromatin immunoprecipitation 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 show the important role of the Bub1b/FoxM1 pathway in RMS and provide potential therapeutic targets.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500453 | PMC |
| http://dx.doi.org/10.1158/0008-5472.CAN-12-1991 | DOI Listing |
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