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Cell Mol Life Sci. 2016 Mar;73(6):1159-72. doi: 10.1007/s00018-015-2112-y. Epub 2015 Dec 19.

FOXO transcription factors in cancer development and therapy.

Author information

1
de Duve Institute, MEXP-UCL 74.30, Université catholique de Louvain, Avenue Hippocrate 75, B1.74.05, 1200, Brussels, Belgium.
2
de Duve Institute, MEXP-UCL 74.30, Université catholique de Louvain, Avenue Hippocrate 75, B1.74.05, 1200, Brussels, Belgium. JB.Demoulin@uclouvain.be.

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:

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

PMID:
26686861
DOI:
10.1007/s00018-015-2112-y
[Indexed for MEDLINE]

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