Numerous studies have indicated that the activation of Notch1 promotes EMT in HCC, contributing to the acquisition of stem-like characteristics, as well as facilitating migration, invasion, and chemoresistance.343,344 Mechanistically, Xie and colleagues have noted that tetraspanin5 activates Notch signaling by enhancing the γ-secretase-catalyzed cleavage of the Notch1 receptor.345 This activation further promotes EMT and rearrangement of the actin cytoskeleton, ultimately fostering the metastasis of HCC. The gene discussed is NOTCH1; the disease is hepatocellular carcinoma.