In CRC, L1CAM is dispensable for adenoma formation, but is activated as tumours progress, in response to the loss of epithelial integrity as a result of the loss of E-cadherin in cell–cell junctions by a mechanism that requires the removal of REST (a regulator of the Polycomb receptor complex 1—PRC1) from an L1CAM enhancer. This evidence concerns the gene L1CAM and colorectal carcinoma.