It seems rather intriguing that the development and maintenance of cancer stemness may be based on the FZD4-dependent regulatory axis involving two protein disulfide isomerases (AGR3-Wnt/β-catenin signaling-AGR2), as it follows from the studies performed on colorectal cancer [269,270]; at least, this may provide additional opportunities for he therapeutic targeting of cancer stemness. This evidence concerns the gene FZD4 and cancer.