L1CAM is a marker and mediator of metastasis initiating cells, which are required for orthotopic carcinoma propagation, liver metastatic colonization and chemoresistance.181,182 L1CAM is induced after loss of epithelial integrity, it then promotes tumor growth and metastasis.183 The mechanism that epithelial cells enter into an L1CAM high phenotypic state is epithelial dissociation causes transcriptional downregulation of REST, in turn reducing REST occupancy of an L1CAM intronic enhancer and promoting L1CAM expression. The gene discussed is REST; the disease is carcinoma.