期刊
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
卷 15, 期 6, 页码 645-652出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijms.23460
关键词
Verteporfin; YAP; bladder cancer; cell growth and invasion
资金
- National Natural Science Foundation of China [81702510, 81702764]
- Planned Science and Technology Project of Guangdong Province, China [2017A020215004, 2017A020215 120]
- China Postdoctoral Foundation [2015M582462]
- Shenzhen Municipal Government of China [ZDSYS2 01504301722174, JCYJ20150330102720130, GJHZ20150 316154912494, JCYJ20160425100840929, JCYJ2017030 6091121656]
- Special Support Funds of Shenzhen for Introduced High-Level Medical Team
- Shenzhen High-Level Medical Discipline Development Program [2016031638]
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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