NOTCH4 and cancer: However, other representative molecules in each pathway were not altered under knockdown or overexpression of LINC02470, including CTNNB1 and TCF-4, which indicate β-catenin signaling activation, NOTCH1 and NOTCH4, two major dysregulated NOTCH ligands, which induce NOTCH signaling activation in cancer development, and SMAD2 and SMAD4, which induce SMAD2/3 signaling activation (Figure 3E–G).