Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 73, Issue 6, Pages 1159-1172Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-015-2112-y
Keywords
FOXO1; FOXO3; FOXO4; Cancer stem cells; Tumor-initiating cells; Cell cycle; Cell invasion; Metastasis
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Funding
- Salus Sanguinis foundation
- Actions de Recherche Concertees'' (Communaute Francaise de Belgique, Belgium)
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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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