Downregulation of β-catenin by human Axin and its association with the APC tumor suppressor, β-catenin and GSK3β

Background: Inactivation of the adenomatous polyposis coli (APC) tumor suppressor protein is responsible for both inherited and sporadic forms of colon cancer. Growth control by APC may relate to its ability to downregulate β-catenin post-translationally. In cancer, mutations in APC ablate its ability to regulate β-catenin, and mutations in β-catenin prevent its downregulation by wild-type APC. Moreover, signaling by the protein product of the wnt-1 proto-oncogene upregulates β-catenin and promotes tumorigenesis in mice. In a Xenopus developmental system, Wnt-1 signaling was inhibited by Axin, the product of the murine fused gene. This suggests a possible link between Axin, the Wnt-1 signaling components β-catenin and glycogen synthase kinase 3β (GSK3β), and APC.