For example, FOXO3 hypermethylation results in the expression of SOX2, which enhances self-renewal and transactivates DNMT1 in a feed-forward loop.30 In CRC, DNMT1 contributes to CSC maintenance by silencing genes involved in differentiation and apoptosis.31,33 Dysregulated DNA methylation can also promote cancer stemness by activating WNT/β-catenin signaling. This evidence concerns the gene SOX2 and cancer.