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A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine

Liver cancer has relatively few early symptoms and is usually diagnosed in the advanced stage. Sorafenib is the only first-line anticancer drug approved by the Food and Drug Administration (FDA) for advanced HCC; however, its use is limited due to resistance. Therefore, the development of new drugs...

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Autores principales: Yun, Un-Jung, Bae, Su-Jin, Song, Yu-Rim, Kim, Young-Woo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837083/
https://www.ncbi.nlm.nih.gov/pubmed/35163776
http://dx.doi.org/10.3390/ijms23031855
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author Yun, Un-Jung
Bae, Su-Jin
Song, Yu-Rim
Kim, Young-Woo
author_facet Yun, Un-Jung
Bae, Su-Jin
Song, Yu-Rim
Kim, Young-Woo
author_sort Yun, Un-Jung
collection PubMed
description Liver cancer has relatively few early symptoms and is usually diagnosed in the advanced stage. Sorafenib is the only first-line anticancer drug approved by the Food and Drug Administration (FDA) for advanced HCC; however, its use is limited due to resistance. Therefore, the development of new drugs is essential to achieving customized treatment. Many studies have suggested that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) is associated with metastasis and cancer formation and progression in various cancers. In the present study, YAP was overexpressed in various patient-derived hepatocarcinoma (HCC) tissues. In addition, this study examined whether evodiamine (which has anticancer effects) can inhibit YAP and, if so, modulate HCC. Evodiamine significantly reduced both the YAP level and cell growth of HCC in a dose-dependent manner. Biochemical analysis indicated mitochondria dysfunction-mediated apoptosis to be the cause of the reduction in HCC cell growth by evodiamine. YAP was overexpressed in metastatic HCC tissues as well when compared to primary HCC tissues. Migration and invasion analysis showed that evodiamine has anti-metastatic ability on Hep3B and Huh-7 cells and reduces the level of vimentin, an EMT marker. In conclusion, YAP is a critical target in HCC therapy, and evodiamine can be an effective HCC anticancer drug by reducing the YAP level.
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spelling pubmed-88370832022-02-12 A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine Yun, Un-Jung Bae, Su-Jin Song, Yu-Rim Kim, Young-Woo Int J Mol Sci Article Liver cancer has relatively few early symptoms and is usually diagnosed in the advanced stage. Sorafenib is the only first-line anticancer drug approved by the Food and Drug Administration (FDA) for advanced HCC; however, its use is limited due to resistance. Therefore, the development of new drugs is essential to achieving customized treatment. Many studies have suggested that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) is associated with metastasis and cancer formation and progression in various cancers. In the present study, YAP was overexpressed in various patient-derived hepatocarcinoma (HCC) tissues. In addition, this study examined whether evodiamine (which has anticancer effects) can inhibit YAP and, if so, modulate HCC. Evodiamine significantly reduced both the YAP level and cell growth of HCC in a dose-dependent manner. Biochemical analysis indicated mitochondria dysfunction-mediated apoptosis to be the cause of the reduction in HCC cell growth by evodiamine. YAP was overexpressed in metastatic HCC tissues as well when compared to primary HCC tissues. Migration and invasion analysis showed that evodiamine has anti-metastatic ability on Hep3B and Huh-7 cells and reduces the level of vimentin, an EMT marker. In conclusion, YAP is a critical target in HCC therapy, and evodiamine can be an effective HCC anticancer drug by reducing the YAP level. MDPI 2022-02-06 /pmc/articles/PMC8837083/ /pubmed/35163776 http://dx.doi.org/10.3390/ijms23031855 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yun, Un-Jung
Bae, Su-Jin
Song, Yu-Rim
Kim, Young-Woo
A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine
title A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine
title_full A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine
title_fullStr A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine
title_full_unstemmed A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine
title_short A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine
title_sort critical yap in malignancy of hcc is regulated by evodiamine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837083/
https://www.ncbi.nlm.nih.gov/pubmed/35163776
http://dx.doi.org/10.3390/ijms23031855
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