However, our findings suggest that ZNRF3/RNF43 deactivation may unleash other key oncogenic pathways in CRC, especially in the context of APC/CTNNB1 co-mutations that bypass the need for WNT receptor activation for pathway activation (Cerami et al. 2012; Gao et al. 2013). Here, ZNRF3 is linked to colorectal carcinoma.