Some studies show that the activation of SHH signaling can facilitate the proliferation, invasion, or angiogenesis of the tumors,21, 22 however, most studies stress their emphasis on the effects of SHH as a proto oncoprotein of the tumor cells,23, 24, 25 and data on the importance of SHH in the CAFs—tumor cell crosstalk is sparse at best. This evidence concerns the gene SHH and neoplasm.