APC controls Wnt-induced beta-catenin destruction complex recruitment in human colonocytes

Wnt/beta -catenin signaling is essential for intestinal homeostasis and is aberrantly activated in most colorectal cancers (CRC) through mutation of the tumor suppressor Adenomatous Polyposis Coli (APC). APC is an essential component of a cytoplasmic protein complex that targets beta -catenin for destruction. Following Wnt ligand presentation, this complex is inhibited. However, a role for APC in this inhibition has not been shown. Here, we utilized Wnt3a-beads to locally activate Wnt co-receptors. In response, the endogenous beta -catenin destruction complex reoriented toward the local Wnt cue in CRC cells with full-length APC, but not if APC was truncated or depleted. Non-transformed human colon epithelial cells displayed similar Wnt-induced destruction complex localization which appeared to be dependent on APC and less so on Axin. Our results expand the current model of Wnt/beta -catenin signaling such that in response to Wnt, the beta -catenin destruction complex: (1) maintains composition and binding to beta -catenin, (2) moves toward the plasma membrane, and (3) requires full-length APC for this relocalization.