title: Forkhead box M1 is regulated by heat shock factor 1 and promotes glioma cells survival under heat shock stress.
abstract: The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology. Prior studies have shown that FoxM1 is overexpressed in a variety of human tumors, including brain tumor, and plays a critical role in cancer development and progression. In this study we found that FoxM1 was up-regulated by heat shock factor 1 (HSF1) under heat shock stress condition in multiple cell lines. Knockdown of HSF1 with HSF1 siRNA or inhibition of HSF1 with a HSF1 inhibitor abrogated heat shock-induced expression of FoxM1. Genetic deletion of HSF1 in mouse embryo fibroblast cells also abolished heat shock stress-induced FoxM1 expression. Moreover, we showed that HSF1 directly bound to FoxM1 promoter and increased FoxM1 promoter activity. Furthermore, we demonstrated that FoxM1 was required for the G(2)-M phase progression through regulating Cdc2, Cdc20, and Cdc25B under a mild heat shock stress but enhanced cell survival under lethal heat shock stress condition. Finally, in human glioblastoma specimens, FoxM1 overexpression correlated with elevated HSF1 expression. Our results indicate that FoxM1 is regulated by HSF1 and is critical for HSF1-mediated heat shock response. We demonstrated a novel mechanism of stress resistance controlled by HSF1 and a new HSF-FoxM1 connection that mediates cellular thermotolerance.
authors.affiliation: Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Dai
authors.forename: Aihua
authors.initials: A
authors.lastname: Gong
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Jing
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
authors.forename: Shin-Hyuk
authors.initials: SH
authors.lastname: Kang
authors.forename: Raymond
authors.initials: R
authors.lastname: Sawaya
authors.forename: Suyun
authors.initials: S
authors.lastname: Huang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C491524:Foxm1 protein, mouse; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D034741:RNA, Small Interfering; D014157:Transcription Factors