Combined with its ability to stabilize p-PI3K levels and reduce p-Akt levels, SPINK13 might downregulate the Notch1/Hes1/PTEN/Akt signaling pathway through the inhibition of Furin activity, thereby reversing the epithelial-mesenchymal transition (EMT) state of HCC cells and inducing apoptosis and cell cycle arrest (Fig. 7G). Here, HES1 is linked to hepatocellular carcinoma.