Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)-positive CSCs, promoting HCC and showing marked sorafenib-resistance, expressed high levels of lysine-specific demethylase-1 (LSD1/KDM1A), which inhibited expression of several β-catenin suppressors, such as APC and Prickle 1 by regulating mono- and di-methylation of histone H3 lysine-4 as the promoters of these genes, and thereby augmented β-catenin activation [81]. This evidence concerns the gene LGR5 and hepatocellular carcinoma.