Figure 3. Canonical Wnt–β-catenin signalling in pancreatic ductal adencocarcinoma.

a | In normal development, canonical Wnt–β-catenin signalling depends on secreted ligands (Wnt ligands) that activate receptors (Frizzled (Fzd)–Lrp complex) that block the proteosomal degradation of β-catenin promoted by the destruction complex (comprising adeomatous polyposis coli (APC), axin, glycogen synthase kinase 3β (GSK3β) and other proteins) through activation of Dishevelled (Dvl). b | β-catenin accumulation is frequently observed in pancreatic ductal adenocarcinoma (PDAC). Accumulated β-catenin can translocate into the nucleus and activate target genes in concert with TCF/LEF co-factors. Presently, the dominant mechanism of persistent β-catenin accumulation and activity in PDAC is unclear. There is evidence for both autocrine (owing to epithelial-derived Wnt ligands) and cell-autonomous activation (through Gli signalling and genes such as ataxia telangiectasia group D-associated (ATDC), which activates Dvl). There may also be contributions from the stromal cells and extracellular matrix that may promote β-catenin accumulation.