Matsumura et al. [161] found that 5-fluorouracil (5-FU) stimulated IFN-mediated signaling pathways in three human ESCC cell lines, which included the upregulation of ISG15 in both the presence and absence of type I IFNs, and reported that IFN-α/β augmented the suppressive effects of 5-FU on ESCC cell growth. Here, ISG15 is linked to esophageal squamous cell carcinoma.