SMAD4 and neoplasm: Notably, E-cadherin and Smad4, the essential mediators of this elimination system, are also tumor-suppressor genes (Christofori and Semb, 1999; Derynck et al., 2001), and loss-of-function of either E-cadherin or Smad4 prevented Wnt/β-catenin-hyperactivated cells from apoptotic elimination in zebrafish (Akieda et al., 2019).