FOXO1 and cancer: Increased HIF1α transcriptional activity in turn activates VEGF-A/neuropilin-1 (NRP1) signaling to upregulate the AKT/FOXO1 pathway, which results in nuclear export of the transcription repressor FOXO1 to induce Twist1-dictated epithelial-to-mesenchymal transition (EMT) and paracrine sonic hedgehog (Shh) signaling, creating a vicious cycle between cancer and stromal cells (16, 23).