The FOXO family comprise four highly related members: FOXO1 (FKHR), FOXO3 (FKHRL1), FOXO4 (AFX) and FOXO6 in mammals, which are orthologs of DAF-16 in Caenorhabditis elegans and dFOXO in Drosophila melanogaster. Mammalian FOXO family members were initially reported as part of pro-oncogenic fusion proteins of paired box protein 3/7 (PAX)-FOXO1 in alveolar rhabdomyosarcoma, whereby FOXO1 trans-activation and the FOXO-dependent TGF-β response was inhibited, thus promoting tumorigenesis (2, 3). This evidence concerns the gene FOXO4 and alveolar rhabdomyosarcoma.