Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors.
Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors.
复制标题
DOI：
10.1016/j.ccell.2014.09.001
复制
发表时间：
2014-10-13
期刊：
影响因子：
50.3
通讯作者：
Beachy PA
中科院分区：
文献类型：
--
作者：
Shin K;Lim A;Zhao C;Sahoo D;Pan Y;Spiekerkoetter E;Liao JC;Beachy PA
Hedgehog（Hh）通路抑制剂在治疗基底细胞癌和成神经管细胞瘤中是临床有效的，但在治疗内胚层来源的结肠癌和胰腺癌中在治疗上失败或甚至加速进展。在膀胱，另一个器官的内胚层起源，我们发现，尽管其最初存在于癌细胞的起源声刺猬（Shh）的表达总是失去进展过程中浸润性尿路上皮癌。此外，对Shh的间质反应的遗传阻断显著加速进展并缩短存活时间。Hh通路活性的这种癌症抑制作用与刺激尿路上皮分化的BMP信号的基质表达相关。低剂量FK506通过药理学激活BMP通路活性显著降低进展，提示了一种管理人膀胱癌的方法。
Hedgehog (Hh) pathway inhibitors are clinically effective in treatment of basal cell carcinoma and medulloblastoma, but fail therapeutically or even 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.
登录
查看更多内容
影响因子：
50.3
作者：
Özdemir BC;Pentcheva-Hoang T;Carstens JL;Zheng X;Wu CC;Simpson TR;Laklai H;Sugimoto H;Kahlert C;Novitskiy SV;De Jesus-Acosta A;Sharma P;Heidari P;Mahmood U;Chin L;Moses HL;Weaver VM;Maitra A;Allison JP;LeBleu VS;Kalluri R
通讯作者：
Kalluri R
影响因子：
64.5
作者：
LIU, J;FARMER, JD;SCHREIBER, SL
通讯作者：
SCHREIBER, SL
影响因子：
10.4
作者：
BRYAN, GT
通讯作者：
BRYAN, GT
影响因子：
11.5
作者：
Kaye, Stanley B.;Fehrenbacher, Louis;Reddy, Josina C.
通讯作者：
Reddy, Josina C.
DOI：
10.1126/stke.2002.151.pe40
发表时间：
2002-09-24
期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
--
作者：
Miyazono, Kohei;Miyazawa, Keiji
通讯作者：
Miyazawa, Keiji