For example, repressive H3K27me3 marks installed by EZH2 are enriched in the Kruppel-like factor 2 (KLF2) promoter, leading to a growth advantage in the tumor cell population in GC and CRC,95,96 via the HIF-1α/Notch-1 signaling pathway and the Hedgehog pathway.97,98 In addition, the proliferation of CRC cells is significantly accelerated by the EZH2-mediated H3K27me3 modification of the dual specificity phosphatase 5 (DUSP5) gene,99 a negative regulator of the mitogen-activated protein kinase (MAPK)-signaling pathway.100. This evidence concerns the gene NOTCH1 and colorectal carcinoma.