Figure 6.

β-catenin in hypoxia and under oxidative stress. (A) Under hypoxic conditions in stem cells activated HIF1α stimulates transcription mediated by β-catenin and Lef1 (and/or TCF1) and by promoting nuclear translocation of β-catenin. (B) In differentiated or cancer cells, HIF1α usurps β-catenin at the expense of TCF/Lef transcription factors, thereby inhibiting Tcf/β-catenin-mediated transcription. β-Catenin potentiates transcription of HIF1α target genes. Among the others targets are the forkhead transcription factors FOXO, which are also upregulated under stress conditions caused by ROS. FOXO transcription factors even sequester β-catenin from TCF/Lef, counteracting TCF/β-catenin-mediated transcription. Growth stimuli (such as Insulin) can activate the protein kinase Akt/PKB, which blocks FOXO activity and may promote phosphorylation of β-catenin, restoring active TCF/β-catenin transcription.