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YAP1 Inhibition in HUVECs Is Associated with Released Exosomes and Increased Hepatocarcinoma Invasion and Metastasis

Hepatocellular carcinoma is one of the most common gastrointestinal malignancies. Anti-angiogenesis therapies have recently demonstrated promise in the treatment of malignancies, although early treatment benefits may be accompanied by metastasis over time. Additional and more effective anti-angiogen...

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Autores principales: Li, Yan, Zhang, Xiaodong, Zheng, Qianqian, Zhang, Yijun, Ma, Yingbo, Zhu, Chen, Yang, Liang, Peng, Xueqiang, Wang, Qi, Wang, Biao, Meng, Xin, Li, Hangyu, Liu, Jingang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281784/
https://www.ncbi.nlm.nih.gov/pubmed/32516736
http://dx.doi.org/10.1016/j.omtn.2020.05.021
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author Li, Yan
Zhang, Xiaodong
Zheng, Qianqian
Zhang, Yijun
Ma, Yingbo
Zhu, Chen
Yang, Liang
Peng, Xueqiang
Wang, Qi
Wang, Biao
Meng, Xin
Li, Hangyu
Liu, Jingang
author_facet Li, Yan
Zhang, Xiaodong
Zheng, Qianqian
Zhang, Yijun
Ma, Yingbo
Zhu, Chen
Yang, Liang
Peng, Xueqiang
Wang, Qi
Wang, Biao
Meng, Xin
Li, Hangyu
Liu, Jingang
author_sort Li, Yan
collection PubMed
description Hepatocellular carcinoma is one of the most common gastrointestinal malignancies. Anti-angiogenesis therapies have recently demonstrated promise in the treatment of malignancies, although early treatment benefits may be accompanied by metastasis over time. Additional and more effective anti-angiogenic treatment modalities are therefore needed. We previously found that Yes-associated protein 1 (YAP1) expression is increased in hepatocellular carcinoma (HCC), particularly around tumor-associated blood vessels, suggesting a role in angiogenesis. The YAP1 inhibitor verteporfin is presently in anti-angiogenic clinical trials for the treatment of various cancers. Depleted YAP1 from vascular endothelial cells effectively reduced proliferation and tube formation, validating its utility as an anti-angiogenesis target. We also showed that YAP1 depletion or inhibition in vascular endothelial cells leads to increased release of exosomes containing the long non-coding RNA (lncRNA) MALAT1 into the tumor microenvironment. Direct exosomal transfer of MALAT1 to hepatic cells leads to increased hepatic cell invasion and migration via activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. These observations may explain the occurrence of distant tumor metastasis with YAP1-associated anti-angiogenic therapy over time. It provides insight into new pathways and treatment paradigms that may be targeted to increase the long-term success of anti-angiogenic therapies.
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spelling pubmed-72817842020-06-11 YAP1 Inhibition in HUVECs Is Associated with Released Exosomes and Increased Hepatocarcinoma Invasion and Metastasis Li, Yan Zhang, Xiaodong Zheng, Qianqian Zhang, Yijun Ma, Yingbo Zhu, Chen Yang, Liang Peng, Xueqiang Wang, Qi Wang, Biao Meng, Xin Li, Hangyu Liu, Jingang Mol Ther Nucleic Acids Article Hepatocellular carcinoma is one of the most common gastrointestinal malignancies. Anti-angiogenesis therapies have recently demonstrated promise in the treatment of malignancies, although early treatment benefits may be accompanied by metastasis over time. Additional and more effective anti-angiogenic treatment modalities are therefore needed. We previously found that Yes-associated protein 1 (YAP1) expression is increased in hepatocellular carcinoma (HCC), particularly around tumor-associated blood vessels, suggesting a role in angiogenesis. The YAP1 inhibitor verteporfin is presently in anti-angiogenic clinical trials for the treatment of various cancers. Depleted YAP1 from vascular endothelial cells effectively reduced proliferation and tube formation, validating its utility as an anti-angiogenesis target. We also showed that YAP1 depletion or inhibition in vascular endothelial cells leads to increased release of exosomes containing the long non-coding RNA (lncRNA) MALAT1 into the tumor microenvironment. Direct exosomal transfer of MALAT1 to hepatic cells leads to increased hepatic cell invasion and migration via activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. These observations may explain the occurrence of distant tumor metastasis with YAP1-associated anti-angiogenic therapy over time. It provides insight into new pathways and treatment paradigms that may be targeted to increase the long-term success of anti-angiogenic therapies. American Society of Gene & Cell Therapy 2020-05-21 /pmc/articles/PMC7281784/ /pubmed/32516736 http://dx.doi.org/10.1016/j.omtn.2020.05.021 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Li, Yan
Zhang, Xiaodong
Zheng, Qianqian
Zhang, Yijun
Ma, Yingbo
Zhu, Chen
Yang, Liang
Peng, Xueqiang
Wang, Qi
Wang, Biao
Meng, Xin
Li, Hangyu
Liu, Jingang
YAP1 Inhibition in HUVECs Is Associated with Released Exosomes and Increased Hepatocarcinoma Invasion and Metastasis
title YAP1 Inhibition in HUVECs Is Associated with Released Exosomes and Increased Hepatocarcinoma Invasion and Metastasis
title_full YAP1 Inhibition in HUVECs Is Associated with Released Exosomes and Increased Hepatocarcinoma Invasion and Metastasis
title_fullStr YAP1 Inhibition in HUVECs Is Associated with Released Exosomes and Increased Hepatocarcinoma Invasion and Metastasis
title_full_unstemmed YAP1 Inhibition in HUVECs Is Associated with Released Exosomes and Increased Hepatocarcinoma Invasion and Metastasis
title_short YAP1 Inhibition in HUVECs Is Associated with Released Exosomes and Increased Hepatocarcinoma Invasion and Metastasis
title_sort yap1 inhibition in huvecs is associated with released exosomes and increased hepatocarcinoma invasion and metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281784/
https://www.ncbi.nlm.nih.gov/pubmed/32516736
http://dx.doi.org/10.1016/j.omtn.2020.05.021
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