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

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 c...

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Autores principales: Feng, Juntao, Gou, Jinhai, Jia, Jia, Yi, Tao, Cui, Tao, Li, Zhengyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010158/
https://www.ncbi.nlm.nih.gov/pubmed/27621651
http://dx.doi.org/10.2147/OTT.S109979
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author Feng, Juntao
Gou, Jinhai
Jia, Jia
Yi, Tao
Cui, Tao
Li, Zhengyu
author_facet Feng, Juntao
Gou, Jinhai
Jia, Jia
Yi, Tao
Cui, Tao
Li, Zhengyu
author_sort Feng, Juntao
collection PubMed
description 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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spelling pubmed-50101582016-09-12 Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer Feng, Juntao Gou, Jinhai Jia, Jia Yi, Tao Cui, Tao Li, Zhengyu Onco Targets Ther Original Research 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. Dove Medical Press 2016-08-29 /pmc/articles/PMC5010158/ /pubmed/27621651 http://dx.doi.org/10.2147/OTT.S109979 Text en © 2016 Feng et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Feng, Juntao
Gou, Jinhai
Jia, Jia
Yi, Tao
Cui, Tao
Li, Zhengyu
Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer
title Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer
title_full Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer
title_fullStr Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer
title_full_unstemmed Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer
title_short Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer
title_sort verteporfin, a suppressor of yap–tead complex, presents promising antitumor properties on ovarian cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010158/
https://www.ncbi.nlm.nih.gov/pubmed/27621651
http://dx.doi.org/10.2147/OTT.S109979
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