Although similar to Itch, over-expression of any of the E3 ligases including NEDD4, WWP1, Smurf1, and Smurf2 causes dose-dependent reduction of LATS1 (Fig. 1A), only siRNA knockdown of WWP1 like that of Itch caused significant increases on endogenous LATS1 levels in breast cancer cells (Fig. 1B), suggesting that Itch and WWP1 are essential E3 ubiquitin ligases regulating stability of LATS1. Here, SMURF2 is linked to breast cancer.