EZH2 and cancer: Because decreased abundance of H3K27me3 is a predictor of cancer aggressiveness independently of the expression of the H3K27me3 methyltransferase EZH2 (Holm et al., 2012; Wei et al., 2008) closely related to the maintenance of poorly differentiated CSC (Sakaki et al., 2015; Yan et al., 2017), our findings suggest that metformin might exert a suppressive influence on the CSC phenotype by enhancing deposition of the repressive H3K27me3 mark.