AXIN2 is a non-redundant regulator of AXIN1 stability and β-catenin in colorectal cancer cells.

Abstract

AXIN proteins are major components of the β-catenin destruction complex or degradasome, which limits β-catenin nuclear translocation and Wnt signalling activation at steady state. Schmidt et al. performed quantitative analysis of cellular AXIN protein levels in human colorectal cancer cells and revealed that AXIN2 plays a non-redundant role in regulating the total AXIN pool and Wnt/β-catenin signalling activity. Tankyrase (TNKS) inhibitors failed to inhibit Wnt/β-catenin signalling in AXIN2 knockout cells, suggesting that AXIN2 is essential for TNKS inhibitors to function. Mechanistically, the authors show that AXIN2 recruits TNKS to AXIN1 and promotes TNKS-mediated degradation of AXIN1. These findings may have important implications for anti-cancer therapy by TNKS small molecule inhibitors.