Similarly, terminally differentiated enterocytes or DCLK1+ tuft-cells re-express ISC markers (Lgr5, Ascl2, Rnf43) and acquire tumour-forming capacity following simultaneous stimulation of Wnt and inflammation pathways, which support a ‘top-down’ model of CRC initiation [171,172]. This evidence concerns the gene RNF43 and colorectal carcinoma.