Role of ion channels in gastrointestinal cancer

Figure 1 Two models for the effect of CFTR deficiency on Wnt/β-catenin signaling. A: CFTR deficiency promotes Wnt/β-catenin signaling. CFTR deficiency causes increased intracellular pH. Increased pH promotes association with Dishevelled (DVL) at the membrane and with the Wnt receptor Frizzled (FZD). DVL association with FZD enhances Wnt/β-catenin signaling leading to increased nuclear localization of β-catenin. Nuclear β-catenin promotes transcription of genes involved in proliferation, survival and stemness[93]; B: CFTR deficiency inhibits Wnt/β-catenin signaling. CFTR deficiency releases membrane associated β-catenin to the cytosol where it is degraded thus decreasing Wnt/β-catenin activity. Loss of β-catenin releases NF-κB which translocates to the nucleus where it promotes transcription of inflammatory targets[145]. FZD: Frizzled; DVL: Dishevelled; AJ: Adherens junctions.