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

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

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Acknowledgements

Fung Zhao is a recipient of a HKU-ICL joint studentship. Eric W.-F. Lam’s work is sponsored by Breast Cancer Campaign, Cancer Research UK, Imperial College NHS Health Trust. We also thank Dr Chuay-Yeng Koo for reading this manuscript and advices.

Conflicts of interest None declared.

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg