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FOXO transcription factors in cancer development and therapy

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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.

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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.

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  1. de Duve Institute, MEXP-UCL 74.30, Université catholique de Louvain, Avenue Hippocrate 75, B1.74.05, 1200, Brussels, Belgium

    Alexandra Coomans de Brachène & Jean-Baptiste Demoulin

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  1. Alexandra Coomans de Brachène
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Coomans de Brachène, A., Demoulin, JB. FOXO transcription factors in cancer development and therapy. Cell. Mol. Life Sci. 73, 1159–1172 (2016). https://doi.org/10.1007/s00018-015-2112-y

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