EPHA2 and breast cancer: To determine the mechanism by which EphA2 is regulated by RNF5 in breast cancers, RNF5 expression was depleted by shRNA in MCF7 and MDA-MB-231 breast cancer cells, and the level of EphA2 protein in the RNF5 knockdown (KD) cells was found to be significantly higher than that in the RNF5 wild-type (WT) cells (Fig. 2A).