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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2016
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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. |
format | Online Article Text |
id | pubmed-5010158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
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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