Their re-expression during serrated tumorigenesis once again points to a switch from the canonical Wnt signaling active during conventional adenomatous tumorigenesis to a fundamentally different variant form of this signaling cascade, as previously discussed for AQP5 and NKD1. Indeed, ZIC5/2 expression has been reported in APC-wildtype and MMR-deficient colon cancer cell lines, but levels were almost undetectable in APC-mutant and MMR-proficient lines [63]. This evidence concerns the gene AQP5 and malignant colon neoplasm.