Unravelling the tumor-suppressive functions of FOXO proteins

Members of the forkhead box O (FOXO) family of transcription factors have been postulated to be tumor suppressors because of their established roles in cell-cycle arrest, apoptosis, DNA-damage repair and scavenging of reactive oxygen species. Recently, several animal model studies have shown that the FOXO proteins are indeed tumor suppressors. Furthermore, FOXO proteins have recently been implicated in the negative regulation of signaling by the hypoxia-inducible factor 1 during vascular development, raising the possibility that the FOXO proteins suppress not only tumor formation but also tumor angiogenesis and, possibly, metastasis. Here, we discuss recent advances in the understanding of the roles of FOXO family members in tumor suppression.