Identification of FoxM1/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma
| Autor: | Sandra Burkett, Vu N. Ngo, Su Young Kim, Xiaolin Wan, Joseph G. Dolan, Javed Khan, Choh Yeung, Louis M. Staudt, Lee J. Helman |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Cell Survival Transplantation Heterologous Mice Nude Cell Cycle Proteins Cell Growth Processes Mice SCID Biology Protein Serine-Threonine Kinases Article Small hairpin RNA Mice Cell Line Tumor Rhabdomyosarcoma medicine Gene Knockdown Techniques Endoreduplication Animals DNA Barcoding Taxonomic Humans RNA Small Interfering Promoter Regions Genetic Mitotic catastrophe Gene knockdown Rh-Hr Blood-Group System Forkhead Box Protein M1 Forkhead Transcription Factors medicine.disease Oncology Cancer research FOXM1 MCF-7 Cells Female Chromatin immunoprecipitation Signal Transduction |
| Zdroj: | Cancer research. 72(22) |
| ISSN: | 1538-7445 |
| Popis: | 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. Cancer Res; 72(22); 5889–99. ©2012 AACR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|