GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:19696738

From GONUTS
Jump to: navigation, search
Citation

Park, HJ, Carr, JR, Wang, Z, Nogueira, V, Hay, N, Tyner, AL, Lau, LF, Costa, RH and Raychaudhuri, P (2009) FoxM1, a critical regulator of oxidative stress during oncogenesis. EMBO J. 28:2908-18

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.

Links

PubMed PMC2760115 Online version:10.1038/emboj.2009.239

Keywords

Animals; Cell Line, Tumor; Cell Transformation, Neoplastic/genetics; Cell Transformation, Neoplastic/metabolism; Forkhead Transcription Factors/genetics; Forkhead Transcription Factors/metabolism; Gene Expression Regulation, Neoplastic; Genes, ras; Humans; Mice; Mice, Inbred C57BL; NIH 3T3 Cells; Osteosarcoma/metabolism; Oxidative Stress; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism; Reactive Oxygen Species/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:Q922T7

involved_in

GO:0000302: response to reactive oxygen species

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:Q922T7

involved_in

GO:0032873: negative regulation of stress-activated MAPK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOXO1

involved_in

GO:0032873: negative regulation of stress-activated MAPK cascade

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOXM1

involved_in

GO:0090344: negative regulation of cell aging

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOXM1

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOXM1

involved_in

GO:0032873: negative regulation of stress-activated MAPK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOXM1

involved_in

GO:0046578: regulation of Ras protein signal transduction

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOXM1

involved_in

GO:0071156: regulation of cell cycle arrest

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOXM1

involved_in

GO:2000377: regulation of reactive oxygen species metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.