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Publication : Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors.

First Author  Shin K Year  2014
Journal  Cancer Cell Volume  26
Issue  4 Pages  521-33
PubMed ID  25314078 Mgi Jnum  J:217892
Mgi Id  MGI:5616026 Doi  10.1016/j.ccell.2014.09.001
Citation  Shin K, et al. (2014) Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors. Cancer Cell 26(4):521-33
abstractText  Hedgehog (Hh) pathway inhibitors are clinically effective in treatment of basal cell carcinoma and medulloblastoma, but fail therapeutically or accelerate progression in treatment of endodermally derived colon and pancreatic cancers. In bladder, another organ of endodermal origin, we find 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 accelerates 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.
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