HES1 and neoplasm: In the regulation of the Notch1 signaling pathway, COE downregulates the mRNA and protein expression of the Notch1 receptor and its downstream target gene Hes1, while upregulating E-cadherin and concurrently downregulating Vimentin and VE-cadherin to effectively inhibit the EMT process, thereby reversing the endothelial-like phenotypic transition of tumor cells (Jue et al., 2017b).