Our previous findings of the invariable loss of Shh in murine and human urothelial carcinomas (Shin et al., 2014b), together with studies of other solid tumors, strongly support a role of Shh as a tumor suppressor during cancer progression (Lee et al., 2014; Rhim et al., 2014; Yang et al., 2017), raising the important questions concerning the molecular mechanisms by which the expression of Shh is lost in tumor cells at early stages of carcinoma development. Here, SHH is linked to urothelial carcinoma.