We thus performed gene operation in mESCC cells, human immortalized normal esophageal epithelial cells (HET-1A) and hESCC cells (KYSE30 and KYSE150) to examine the effects of EFNB1 and EPHB4 on cell malignant phenotypes and found that knocking down either EFNB1 or EPHB4 in cancer cells significantly suppressed cell proliferation but ectopic overexpressing EFNB1 or EPHB4 had opposite effects in both normal and cancer cells (Fig. 4d, e and Supplementary Figs. 5a, b and 6a). Here, EPHB4 is linked to cancer.