4.5 Article

Verteporfin, a suppressor of YAP-TEAD complex, presents promising antitumor properties on ovarian cancer

Journal

ONCOTARGETS AND THERAPY
Volume 9, Issue -, Pages 5371-5381

Publisher

DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S109979

Keywords

YAP; CCN2; ovarian cancer; verteporfin; Hippo pathway

Funding

  1. National Natural Science Foundation of China [81170592, 81101991]
  2. Sichuan Youth Foundation of Science of Technology [2015JQ0026]

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Yes-associated protein (YAP) is a key transcriptional coactivator of Hippo pathway and has been shown to be an oncoprotein in ovarian cancer (OC). Verteporfin (VP), clinically used in photodynamic therapy for neovascular macular degeneration, has been recently proven to be a suppressor of YAP-TEAD complex and has shown potential in anticancer treatment. In this study, we aimed to explore the potential effect of VP in the treatment of OC. Our results showed that VP led to inhibition of proliferation in a time-and dose-dependent manner and to the suppression of migratory and invasive capacities of OC cells. Western blot and real-time polymerase chain reaction demonstrated that VP induced YAP cytoplasmic retention and deregulated inducible YAP and CCNs in OC cells. In vivo, VP exerted a significant effect on tumor growth in OVCAR8 xenograft mice, resulting in tumor nodules with lower average weight and reduced volume of gross ascites. In addition, VP treatment remarkably upregulated cytoplasmic YAP and phosphorylation YAP and downregulated CCN1 and CCN2, but exerted little effect on YAP-upstream components in Hippo pathway. In conclusion, our results suggested that VP may be a promising agent for OC, acting by suppressing YAP-TEAD complex.

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