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Cellular and Molecular Life Sciences

, Volume 73, Issue 6, pp 1159–1172 | Cite as

FOXO transcription factors in cancer development and therapy

  • Alexandra Coomans de Brachène
  • Jean-Baptiste DemoulinEmail author
Review

Abstract

The forkhead box O (FOXO) transcription factors are considered as tumor suppressors that limit cell proliferation and induce apoptosis. FOXO gene alterations have been described in a limited number of human cancers, such as rhabdomyosarcoma, leukemia and lymphoma. In addition, FOXO proteins are inactivated by major oncogenic signals such as the phosphatidylinositol-3 kinase pathway and MAP kinases. Their expression is also repressed by micro-RNAs in multiple cancer types. FOXOs are mediators of the tumor response to various therapies. However, paradoxical roles of FOXOs in cancer progression were recently described. FOXOs contribute to the maintenance of leukemia-initiating cells in acute and chronic myeloid leukemia. These factors may also promote invasion and metastasis of subsets of colon and breast cancers. Resistance to treatment was also ascribed to FOXO activation in multiple cases, including targeted therapies. In this review, we discuss the complex role of FOXOs in cancer development and response to therapy.

Keywords

FOXO1 FOXO3 FOXO4 Cancer stem cells Tumor-initiating cells Cell cycle Cell invasion Metastasis 

Notes

Acknowledgments

This project was supported by grants from Salus Sanguinis foundation and from “Actions de Recherche Concertées” (Communauté Française de Belgique, Belgium). We apologize to authors whose excellent work could not be cited due to space limitation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer International Publishing 2015

Authors and Affiliations

  • Alexandra Coomans de Brachène
    • 1
  • Jean-Baptiste Demoulin
    • 1
    Email author
  1. 1.de Duve Institute, MEXP-UCL 74.30Université catholique de LouvainBrusselsBelgium

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