NOTCH1 and hepatocellular carcinoma: Aberrant Notch signaling (Notch1 and Notch4) promotes self-renewal and metastasis of breast and HCC stem cells.192,193 However, microRNA-34a downregulates Notch1.194 Similarly, abundant Delta-like ligand 4 (DLL4) also promotes tumor angiogenesis and metastasis in gastric CSCs.195 Delta-like 1 activation of Notch1 signaling requires the assistance of the actin-related protein 2/3 complex to maintain the stem cell phenotype of glioma-initiating cells.196 Additionally, some intracellular genes also regulate the Notch signaling pathway.