For example, the CAF-secreted factor transforming growth factor-β,22, 50, 51 mediates epigenetic switches through SOX4 activation, which in turn modulates EZH2, a histone methyltransferase, in cancer cells.52 Furthermore, transforming growth factor-β treatments may induce genome-wide changes in DNA methylation, in liver cancer cell lines.53 Epigenetic players, such as miRNAs,54 also contribute to the maintenance of an invasive, cancer initiating cell phenotype. This evidence concerns the gene EZH2 and cancer.