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

Xiaolin Wan, Choh Yeung, Su Young Kim, Joseph G. Dolan, Vu N. Ngo, Sandra Burkett, Javed Khan, Louis M. Staudt, Lee J. Helman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)5889-5899
Number of pages11
JournalCancer Research
Volume72
Issue number22
DOIs
StatePublished - Nov 15 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wan, X., Yeung, C., Kim, S. Y., Dolan, J. G., Ngo, V. N., Burkett, S., Khan, J., Staudt, L. M., & Helman, L. J. (2012). Identification of FoxM1/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma. Cancer Research, 72(22), 5889-5899. https://doi.org/10.1158/0008-5472.CAN-12-1991