NEDD4 and cancer: To further investigate whether Cdh1 could also control the E3 ligase activity of these Cdh1-interacting NEDD4 family of E3 ligases, we depleted endogenous Cdh1 in multiple cancer cell lines (Figure 1b and c and Supplementary Figure S1a and c) and examined the protein levels of NEDD4 family members interacting with Cdh1.