HES1 and Familial prostate cancer: Colorectal cancer-associated myofibroblasts activate Hes1 through the secretion of IL-6 and IL-8, promoting the expansion of CD133 (+) and CD44 (+) CSCs and suppressing immune cell activity (79); in a hypoxic microenvironment, HIF-1α activates the Notch1/Hes1 pathway, inducing the transformation of prostate cancer cells into a stem cell phenotype (141).