title: FoxM1 in tumorigenicity of the neuroblastoma cells and renewal of the neural progenitors.
abstract: Malignant neuroblastomas contain stem-like cells. These tumors also overexpress the Forkhead box transcription factor FoxM1. In this study, we investigated the roles of FoxM1 in the tumorigenicity of neuroblastoma. We showed that depletion of FoxM1 inhibits anchorage-independent growth and tumorigenicity in mouse xenografts. Moreover, knockdown of FoxM1 induces differentiation in neuroblastoma cells, suggesting that FoxM1 plays a role in the maintenance of the undifferentiated progenitor population. We showed that inhibition of FoxM1 in malignant neuroblastoma cells leads to the downregulation of the pluripotency genes sex determining region Y box 2 (Sox2) and Bmi1. We provided evidence that FoxM1 directly activates expression of Sox2 in neuroblastoma cells. By using a conditional deletion system and neurosphere cultures, we showed that FoxM1 is important for expression of Sox2 and Bmi1 in the mouse neural stem/progenitor cells and is critical for its self-renewal. Together, our observations suggested that FoxM1 plays an important role in the tumorigenicity of the aggressive neuroblastoma cells through maintenance of the undifferentiated state.
authors.affiliation: Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607-7170, USA.
authors.forename: Zebin
authors.initials: Z
authors.lastname: Wang
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Park
authors.forename: Janai R
authors.initials: JR
authors.lastname: Carr
authors.forename: Yi-ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Angela L
authors.initials: AL
authors.lastname: Tyner
authors.forename: Robert H
authors.initials: RH
authors.lastname: Costa
authors.forename: Srilata
authors.initials: S
authors.lastname: Bagchi
authors.forename: Pradip
authors.initials: P
authors.lastname: Raychaudhuri
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000502:physiology*; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000502:physiology*; D009447:Neuroblastoma / Q000209:etiology* / Q000473:pathology; D011401:Promoter Regions, Genetic; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000502:physiology
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors