Downregulation of p120^CTN and β-catenin by ET-1. Lysates normalized for protein content were analyzed for p120^CTN and β-catenin protein levels were analyzed using immunoblots (internal controls for a and b are shown in Figure 1a). (a) ET-1 downregulates p120^CTN. Both large and small isoforms of p120^CTN are present. (b) ET-1 downregulates β-catenin. (c) BQ788 blocks downregulation of p120^CTN (left panel, data shown for melanoma cells) and β-catenin (right panel, data shown for melanocytes) by ET-1. (d) β-catenin Northern blot. GAPDH serves as an internal control. Identical results were obtained using melanoma cells (data not shown). (e) Cell-permeable inhibitors of caspase-8 block downregulation of E-cadherin by ET-1. SKMEL28 cells were untreated (–) or treated (+) with 10 nM ET-1. A variety of caspase inhibitors at 1 nM (upper panel) and 10 nM (lower panel) concentrations were added 34 hours after ET-1 stimulation, and cells were harvested at 40 hours. Samples were examined for E-cadherin protein levels as described previously. (f) A cell-permeable inhibitor of caspase-8 blocks downregulation of E-cadherin, β-catenin, and p120^CTN in FM2030 cells. Identical results were obtained using melanoma cells (data not shown). Results shown are representative of at least four independent experiments. β-cat, β-catenin.