In CSCs, many intracellular signalling pathways, including the TGF-β, Wnt/β-catenin, Notch and NF-κB pathways53, are activated by the CSC microenvironment constituents, including cytokines, chemokines, growth factors and cancer-associated fibroblast54, upon which they transduce signals to transcriptional regulators, including SNAIL, TWIST and ZEB, and EMT effectors such as E-cadherin and vimentin55. This evidence concerns the gene TWIST1 and cancer.