Understanding FOXO, new views on old transcription factors.

FOXO proteins are evolutionarily conserved transcription factors implicated in several fundamental cellular processes, functioning as end-point for transcriptional programs involved in apoptosis, stress response and longevity. Abrogation of FOXO function is very frequent in human cancer, therefore the mechanisms of regulation of the FOXO proteins are receiving increasing attention in cancer research. The FOXO proteins integrate regulatory inputs from a variety of upstream signaling pathways, most importantly in response to growth factor and stress signalling. Recently, FOXO factors have been established as tumor suppressors, promoting the transcription of pro-apoptotic molecules like FasL and Bim when the PI3K/Akt pathway is downregulated due to nutrient or serum starvation and cellular stress. Therefore, understanding the modulation of FOXO transcription factors will allow the design of new compounds with antitumor potential.