RNF43 and cholangiocarcinoma: Loss of function mutations in RNF43 that, therefore, promote Wnt signalling through failing to downregulate the receptor following stimulation thus allow the Fzd receptor to be hyperactivated.63 Despite the lack of core mutations, it remains that there is a high level of canonical Wnt activity in sporadic CC, typified by high levels of nuclear b-catenin of CC cells in ~ 76% of cases.