ZNRF3 and neoplasm: However, in tumors containing activating mutations in CTNNB1 like those engineered into our CTNNB1ST-A cell line, or mutations in the ZNRF3 or RNF43 tumor suppressors, all of which result in hyperactive WNT signaling in the presence of a functional destruction complex, phenocopying the effects of HUWE1 loss may reduce WNT signaling enough to provide a therapeutic benefit.