Verteporfin inhibits YAP-induced bladder cancer cell growth and invasion via Hippo signaling pathway

被引:77
作者
Dong, Liang [1 ,2 ]
Lin, Fan [1 ,3 ]
Wu, Wanjun [1 ]
Liu, Yuchen [1 ]
Huang, Weiren [1 ]
机构
[1] Shenzhen Univ, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Hlth Sci Ctr,State Engn Lab Med Key Technol Appli, Shenzhen 518039, Peoples R China
[2] City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Hong Kong, Peoples R China
[3] Shantou Univ, Guangdong Prov Key Lab Marine Biotechnol, Shantou 515063, Peoples R China
基金
中国国家自然科学基金;
关键词
Verteporfin; YAP; bladder cancer; cell growth and invasion; LIGHT ACTIVATION; APOPTOSIS; TEAD;
D O I
10.7150/ijms.23460
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:645 / 652
页数:8
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