NUAK1 regulates mTOR location and lysosome positioning and directly phosphorylates Akt at Ser-473, and according to its subcellular localization, induces the Akt/ FOXO1-3a axis. NUAK1 promotes cancer cell survival through these mechanisms, and its inhibition potentiated Akt and mTOR pharmacological inhibition. Here, FOXO1 is linked to cancer.