title: FOXO transcription factors in cancer development and therapy.
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.
authors.affiliation: de Duve Institute, MEXP-UCL 74.30, Université catholique de Louvain, Avenue Hippocrate 75, B1.74.05, 1200, Brussels, Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Coomans de Brachène
authors.affiliation: de Duve Institute, MEXP-UCL 74.30, Université catholique de Louvain, Avenue Hippocrate 75, B1.74.05, 1200, Brussels, Belgium. JB.Demoulin@uclouvain.be.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Demoulin
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D019008:Drug Resistance, Neoplasm; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; C108803:FOXO4 protein, human; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D014157:Transcription Factors
keywords: Cancer stem cells; Cell cycle; Cell invasion; FOXO1; FOXO3; FOXO4; Metastasis; Tumor-initiating cells