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Author (up) Maachani, U.B.; Shankavaram, U.; Kramp, T.; Tofilon, P.J.; Camphausen, K.; Tandle, A.T. url  doi
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  Title FOXM1 and STAT3 interaction confers radioresistance in glioblastoma cells Type Journal Article
  Year 2016 Publication Oncotarget Abbreviated Journal Oncotarget  
  Volume 7 Issue 47 Pages 77365-77377  
  Keywords Foxm1; Stat3; glioblastoma multiforme; glioma stem cells; radio resistance  
  Abstract Glioblastoma multiforme (GBM) continues to be the most frequently diagnosed and lethal primary brain tumor. Adjuvant chemo-radiotherapy remains the standard of care following surgical resection. In this study, using reverse phase protein arrays (RPPAs), we assessed the biological effects of radiation on signaling pathways to identify potential radiosensitizing molecular targets. We identified subsets of proteins with clearly concordant/discordant behavior between irradiated and non-irradiated GBM cells in vitro and in vivo. Moreover, we observed high expression of Forkhead box protein M1 (FOXM1) in irradiated GBM cells both in vitro and in vivo. Recent evidence of FOXM1 as a master regulator of metastasis and its important role in maintaining neural, progenitor, and GBM stem cells, intrigued us to validate it as a radiosensitizing target. Here we show that FOXM1 inhibition radiosensitizes GBM cells by abrogating genes associated with cell cycle progression and DNA repair, suggesting its role in cellular response to radiation. Further, we demonstrate that radiation induced stimulation of FOXM1 expression is dependent on STAT3 activation. Co-immunoprecipitation and co-localization assays revealed physical interaction of FOXM1 with phosphorylated STAT3 under radiation treatment. In conclusion, we hypothesize that FOXM1 regulates radioresistance via STAT3 in GBM cells. We also, show GBM patients with high FOXM1 expression have poor prognosis. Collectively our observations might open novel opportunities for targeting FOXM1 for effective GBM therapy.  
  Address Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1949-2553 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27764801 Approved no  
  Call Number ref @ user @ Serial 96631  
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