CRC cell fate is governed by an intricate network of signaling pathways that intersect with epigenetic regulators at the chromatin level.72 In this context, we and other groups have provided evidence of the relevance of epigenetic factors in cancer stemness.17,73 In particular, we hypothesized that SMYD3 can contribute to the maintenance of the CSC state, acting not only by regulating the expression of stemness genes but also through functional interactions and direct methylation of stemness proteins. This evidence concerns the gene PROS1 and cancer.