Figure 2. Membrane localization of PTEN is restored by WWP1 depletion, which increases the sensitivity of the PI3K inhibitor.

(A) Membrane and cytosol fractions isolated from MDA-MB-231 cells stably expressing WWP1 shRNA (shWWP1) or scrambled (shScr). Cells were treated with DMSO or BKM120 for 48 hours. (B) Subcellular fraction of MCF7 cells stably expressing shWWP1 or shScr. Cells were treated with DMSO or 1 μM BYL719 for 48 hours. (C) Analysis of endogenous PTEN ubiquitination in MDA-MB-231 cells with WWP1 shRNA, which were treated with DMSO or BKM120 for 48 hours. (D) Evaluation of the IC₅₀ of breast cancer cells with WWP1 depletion. The relative IC₅₀ ratio was determined by dividing each IC₅₀ value by that of the shScr. The PTEN expression status of each cell was evaluated by WB.