Tankyrase inhibitors, which are potential therapeutics in WNT-dependent cancers, induce cytoplasmic puncta (degradasomes) consisting of components of the signal-limiting WNT/β-catenin destruction complex. 3D structured illumination microscopy of SW480 colon carcinoma cells reveals an irregular shape of the induced degradasomes and a non-homogeneous distribution of tankyrase (green), β-catenin (white) and AXIN2 (red) in subdomains. Nuclei are in blue. Thorvaldsen and colleagues (p. 1487), demonstrate that β-catenin is rapidly turned over in degradasomes upon tankyrase inhibition and provide a direct mechanistic link between degradasome formation and reduced WNT signaling in colon carcinoma cells.