Lineage tracing experiments have shown that LGR5+ cancer cells are capable of self-renewing and generate differentiated cell progeny; LGR5+ cells play an essential role in the growth of human colorectal cancers, however, upon depletion LGR5+ cells are replaced by new LGR5+ cells, originated from the de-differentiation of KRT20+ cells [403]. This evidence concerns the gene LGR5 and colorectal cancer.