CDH1 and neoplasm: Furthermore, during tumor progression, owing to attenuated APCCdh1 activity by Cdk phosphorylation, various APCCdh1 substrates including cyclins and mitotic kinases are accumulated, which not only leads to further suppression of APCCdh1 activity, but possibly also triggers Cdh1 destruction by SCFβ-TRCP [41] to release WWP2 E3 ligase activity for PTEN degradation and subsequent PI3K/Akt activation.