Hedgehog Signaling Restrains Bladder Cancer Progression by Eliciting Stromal Production of Urothelial Differentiation Factors

被引：172

作者：

Shin, Kunyoo ^{[1
,4
]}

Lim, Agnes ^{[1
,3
,4
]}

Zhao, Chen ^{[1
,2
,4
]}

Sahoo, Debashis ^{[1
,5
]}

Pan, Ying ^{[6
,8
]}

Spiekerkoetter, Edda ^{[7
]}

Liao, Joseph C. ^{[6
,8
]}

Beachy, Philip A. ^{[1
,2
,3
,4
]}

机构：

[1] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA

[5] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA

[6] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA

[7] Stanford Univ, Sch Med, Dept Med, Vera Moulton Wall Ctr Pulm Vasc Dis,Cardiovasc In, Stanford, CA 94305 USA

[8] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA

来源：

CANCER CELL | 2014年 / 26卷 / 04期

关键词：

SONIC HEDGEHOG; HUMAN HOMOLOG; STEM-CELLS; BASAL; INHIBITION; INDUCTION; PATHWAY; MEDULLOBLASTOMA; PROLIFERATION; PATHOGENESIS;

D O I：

10.1016/j.ccell.2014.09.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：521 / 533

页数：13

共 51 条

[1] In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog [J].