Our study revealed a provocative role of Hedgehog (Hh) signaling in the progression of bladder cancer, which was published Oct 13 in Cancer Cell (Shin, Beachy Cancer Cell 2014). Hh pathway inhibitors are clinically effective in treatment of basal cell carcinoma and medulloblastoma, but fail therapeutically or even accelerate progression in treatment of colon and pancreatic cancers. In another endodermal organ, the bladder, we found that despite its initial presence in the cancer cell of origin, Sonic hedgehog (Shh) expression is invariably lost during progression to invasive urothelial carcinoma. Genetic blockade of stromal response to Shh furthermore dramatically accelerated progression and decreases survival time. This cancer-restraining effect of Hh pathway activity is associated with stromal expression of BMP signals, which stimulate urothelial differentiation. Progression is dramatically reduced by pharmacological activation of BMP pathway activity with low-dose FK506, suggesting an approach to management of human bladder cancer.