Recent studies have shown that a soft matrix promotes histone modifications to induce the expression of the stemness‐related gene Sox2 in melanoma cells[5] and pluripotency‐related genes in mesenchymal stem cells.[35] To explore the mechanism by which a soft matrix controls the CD133 and/or THBS2 expression, we investigated the differences in H3 modifications between HCC cells cultured on soft and stiff matrixes using a histone H3 modification multiplex assay kit that detects and quantifies 21 modified histone H3 patterns (Figure 6F). This evidence concerns the gene PROM1 and melanoma.