Verteporfin inhibits YAP-induced bladder cancer cell growth and invasion via Hippo signaling pathway.
Verteporfin inhibits YAP-induced bladder cancer cell growth and invasion via Hippo signaling pathway.
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维替泊芬通过 Hippo 信号通路抑制 YAP 诱导的膀胱癌细胞生长和侵袭
DOI：
10.7150/ijms.23460
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发表时间：
2018
影响因子：
3.6
通讯作者：
Huang W
中科院分区：
文献类型：
--
作者：
Dong L;Lin F;Wu W;Liu Y;Huang W
高度保守的Hippo信号通路是参与肿瘤发生和进展的最重要通路之一。前期研究表明，Hippo通路转录共激活因子YAP在临床多种膀胱癌组织中高表达，在膀胱癌进展中发挥着至关重要的作用。为了寻找YAP特异性靶药物及其治疗膀胱癌的分子机制，我们应用YAP特异性抑制剂维替泊芬（VP）作为抗膀胱癌药物，发现VP能够以剂量依赖性方式抑制膀胱癌细胞的生长和侵袭。此外，我们证明VP可以通过抑制Hippo信号通路靶基因的表达来抑制膀胱癌细胞的生长和侵袭。在进一步的研究中，我们提供证据表明VP能够抑制过量YAP诱导的膀胱癌细胞的生长和侵袭。为了解决膀胱癌中VP对YAP的抑制作用，我们检查了靶基因的表达，发现VP可以显着抑制YAP过表达诱导的Hippo通路靶基因的表达。综上所述，我们发现VP通过抑制Hippo信号通路靶基因的表达来抑制YAP诱导的膀胱癌细胞的生长和侵袭。
The highly conserved Hippo signaling pathway is one of the most important pathways involved in tumorigenesis and progress. Previous studies show that YAP, the transcriptional coactivator of Hippo pathway, is expressed highly in many clinical bladder cancer tissues and plays crucial role on bladder cancer progress. To find the YAP-specific target drug and its molecular mechanism in bladder cancer, we apply Verteporfin (VP), a YAP specific inhibitor to function as anti-bladder cancer drug and discover that VP is able to inhibit bladder cancer cell growth and invasion in a dosage dependent manner. Moreover, we demonstrate that VP may inhibit bladder cancer cell growth and invasion via repressing target genes' expression of the Hippo signaling pathway. In further study, we provide evidence that VP is able to inhibit excessive YAP induced bladder cancer cell growth and invasion. To address the repressive function of VP against YAP in bladder cancer, we check the target genes' expression and find VP can dramatically repress YAP overexpression induced Hippo pathway target genes' expression. Taken together, we discover that VP inhibits YAP-induced bladder cancer cell growth and invasion via repressing the target genes' expression of Hippo signaling pathway.
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