WWP2 and neoplasm: As elevated Cdk2/cyclin A and Cdk2/cyclin E activities, which are tightly associated with tumorigenesis, has been reported to dissociate Cdh1 from the APC core complex [29], it is possible that in tumor cell settings, a large portion of Cdh1 exists in an APC-free mode to modulate tumorigenesis by governing the WWP2/PTEN/Akt signaling axis (Figure 6 and Supplementary Figure S6).