FoxM1, a critical regulator of oxidative stress during oncogenesis

Hyun Jung Park, Janai R. Carr, Zebin Wang, Veronique Nogueira, Nissim Hay, Angela L. Tyner, Lester F. Lau, Robert H. Costa, Pradip Raychaudhuri

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

The transcription factor FoxM1 is over-expressed in most human malignancies. Although it is evident that FoxM1 has critical functions in tumour development and progression, the mechanisms by which FoxM1 participates in those processes are not understood. Here, we describe an essential role of FoxM1 in the regulation of oxidative stress that contributes to malignant transformation and tumour cell survival. We identify a negative feedback loop involving FoxM1 that regulates reactive oxygen species (ROS) in proliferating cells. We show that induction of FoxM1 by oncogenic Ras requires ROS. Elevated FoxM1, in turn, downregulates ROS levels by stimulating expression of ROS scavenger genes, such as MnSOD, catalase and PRDX3. FoxM1 depletion sensitizes cells to oxidative stress and increases oncogene-induced premature senescence. Moreover, tumour cells expressing activated AKT1 are addicted to FoxM1, as they require continuous presence of FoxM1 for survival. Together, our results identify FoxM1 as a key regulator of ROS in dividing cells, and provide insights into the mechanism how tumour cells use FoxM1 to control oxidative stress to escape premature senescence and apoptosis.

Original languageEnglish (US)
Pages (from-to)2908-2918
Number of pages11
JournalEMBO Journal
Volume28
Issue number19
DOIs
StatePublished - Aug 21 2009
Externally publishedYes

Fingerprint

Oxidative stress
Reactive Oxygen Species
Carcinogenesis
Oxidative Stress
Tumors
Cells
Neoplasms
Oncogenes
Catalase
Cell Survival
Transcription Factors
Down-Regulation
Genes
Apoptosis
Feedback
Survival

Keywords

  • Forkhead box transcription factor
  • Oxidative stress
  • Proliferation
  • Reactive oxygen species
  • Tumourigenesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Park, H. J., Carr, J. R., Wang, Z., Nogueira, V., Hay, N., Tyner, A. L., ... Raychaudhuri, P. (2009). FoxM1, a critical regulator of oxidative stress during oncogenesis. EMBO Journal, 28(19), 2908-2918. https://doi.org/10.1038/emboj.2009.239

FoxM1, a critical regulator of oxidative stress during oncogenesis. / Park, Hyun Jung; Carr, Janai R.; Wang, Zebin; Nogueira, Veronique; Hay, Nissim; Tyner, Angela L.; Lau, Lester F.; Costa, Robert H.; Raychaudhuri, Pradip.

In: EMBO Journal, Vol. 28, No. 19, 21.08.2009, p. 2908-2918.

Research output: Contribution to journalArticle

Park, HJ, Carr, JR, Wang, Z, Nogueira, V, Hay, N, Tyner, AL, Lau, LF, Costa, RH & Raychaudhuri, P 2009, 'FoxM1, a critical regulator of oxidative stress during oncogenesis', EMBO Journal, vol. 28, no. 19, pp. 2908-2918. https://doi.org/10.1038/emboj.2009.239
Park HJ, Carr JR, Wang Z, Nogueira V, Hay N, Tyner AL et al. FoxM1, a critical regulator of oxidative stress during oncogenesis. EMBO Journal. 2009 Aug 21;28(19):2908-2918. https://doi.org/10.1038/emboj.2009.239
Park, Hyun Jung ; Carr, Janai R. ; Wang, Zebin ; Nogueira, Veronique ; Hay, Nissim ; Tyner, Angela L. ; Lau, Lester F. ; Costa, Robert H. ; Raychaudhuri, Pradip. / FoxM1, a critical regulator of oxidative stress during oncogenesis. In: EMBO Journal. 2009 ; Vol. 28, No. 19. pp. 2908-2918.
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