Our present study, together with reports from other labs, indicates that Hh activity in colorectal cancer tissues is stimulated by two distinct manners: (i) canonical and Smo-dependent activation of Hh activity in colorectal cancer cells and stromal cells [8–14], and (ii) non-canonical and Smo-independent activation provoked by PGE2 in colorectal cancer cells (Fig. 5D). The gene discussed is SMO; the disease is colorectal cancer.