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Cancer Res. 2012 Nov 15;72(22):5889-99. doi: 10.1158/0008-5472.CAN-12-1991. Epub 2012 Sep 20.

Identification of FoxM1/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma.

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1
Molecular Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. xiaolinw@mail.nih.gov

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.

PMID:
23002205
PMCID:
PMC3500453
DOI:
10.1158/0008-5472.CAN-12-1991
[Indexed for MEDLINE]
Free PMC Article
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