Genes: APC (Adenomatous polyposis coli)

Wnt signaling in the small intestine
Wnt signaling in the small intestine
  • Loss of function can contribute to the development of Familial adenomatous polyposis (FAP)
  • Together with GSK-3β and axin Apc builds the β-catenin destruction complex, which playes a key role in the wnt-signalling pathway.
  • In colonic crypts, Apc negatively controls the levels of β-catenin, which governs the proliveration of the enterocytes in the crypt:
    • Cells are produced at the bottom of the crypt and migrate upward to the villus.
    • β-catenin levels decrease coninously from the lower crypt to the upper villus. This is because the migrating cells increase the expression of APC which, in the absence of Wnts, is able to break down β-catenin.
    • The absence of β-catenin drives cells to differentiation.
    • If APC is mutated and therefore not able to build the β-catenin destruction complex, β-catenin levels stay high and prevent cells from differentiation.
    • Continuous proliferation and the formation of polyps is the consequence.