FoxM1 in tumorigenicity of the neuroblastoma cells and renewal of the neural progenitors

Zebin Wang, Hyun Jung Park, Janai R. Carr, Yi Ju Chen, Yu Zheng, Jing Li, Angela L. Tyner, Robert H. Costa, Srilata Bagchi, Pradip Raychaudhuri

Research output: Contribution to journalArticle

54 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4292-4302
Number of pages11
JournalCancer Research
Volume71
Issue number12
DOIs
StatePublished - Jun 15 2011
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'FoxM1 in tumorigenicity of the neuroblastoma cells and renewal of the neural progenitors'. Together they form a unique fingerprint.

  • Cite this

    Wang, Z., Park, H. J., Carr, J. R., Chen, Y. J., Zheng, Y., Li, J., Tyner, A. L., Costa, R. H., Bagchi, S., & Raychaudhuri, P. (2011). FoxM1 in tumorigenicity of the neuroblastoma cells and renewal of the neural progenitors. Cancer Research, 71(12), 4292-4302. https://doi.org/10.1158/0008-5472.CAN-10-4087