Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

doi:10.1007/s11684-012-0228-0

Front Med

2012, Vol. 6

Issue (4) : 376-380 https://doi.org/10.1007/s11684-012-0228-0

REVIEW

Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

Fung Zhao, Eric W.-F. Lam(

)

Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK

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Abstract

The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance. Recent research shows that the forkhead transcription factor FOXM1 is a direct transcriptional target repressed by the forkhead protein FOXO3a, a vital downstream effector of the PI3K-AKT-FOXO signaling pathway. Intriguingly, FOXM1 and FOXO3a also compete for binding to the same gene targets, which have a role in chemotherapeutic drug action and sensitivity. An understanding of the role and regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of chemotherapeutic drug action and resistance in patients, and provide new insights into the design of novel therapeutic strategy and reliable biomarkers for prediction of drug sensitivity.

Keywords FOXO3a FOXM1 transcription factor cancer drug resistance tumorigenesis

Corresponding Author(s): Lam Eric W.-F.,Email:eric.lam@imperial.ac.uk

Issue Date: 05 December 2012

Cite this article:

Fung Zhao,Eric W.-F. Lam. Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance[J]. Front Med, 2012, 6(4): 376-380.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-012-0228-0
https://academic.hep.com.cn/fmd/EN/Y2012/V6/I4/376

Fig.1 Integration of signals with FOXO and FOXM1 axis upon stimulation of chemotherapeutic drugs. Hemotherapeutic drugs have various modes of action but ultimately integrate signals with the PI3K-AKT-FOXO-FOXM1 signaling cascade. FOXO and FOXM1 then exert antagonistic functions in the regulation of target genes, which in turn control cancer-related processes including drug resistance, angiogenesis and migration.

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