ISG15 and breast cancer: For example, in basal breast cancer cells, ISG15 promotes tumor cell growth by maintaining the activation of the PI3K/AKT pathway through the inhibition of the formation of a complex between GDP dissociation inhibitor 2 and the epidermal growth factor receptor (EGFR) endocytic regulator Rab5 with ISGylation, thus reducing the ratio of EGFR transported to the Golgi body [7].