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YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA

Hepatocellular carcinoma (HCC) is a typical hypervascular solid tumor that requires neoangiogenesis for growth. The vascular endothelial growth factor (VEGF) is the most potent proangiogenic factor in neovascularization. The multifunctional Yin-Yang 1 (YY1) is involved in the regulation of tumor mal...

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Autores principales: Yang, Wendong, Li, Zhongwei, Qin, Rong, Wang, Xiaorui, An, Huihui, Wang, Yule, Zhu, Yan, Liu, Yantao, Cai, Shijiao, Chen, Shuang, Sun, Tao, Meng, Jing, Yang, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868052/
https://www.ncbi.nlm.nih.gov/pubmed/31799179
http://dx.doi.org/10.3389/fonc.2019.01187
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author Yang, Wendong
Li, Zhongwei
Qin, Rong
Wang, Xiaorui
An, Huihui
Wang, Yule
Zhu, Yan
Liu, Yantao
Cai, Shijiao
Chen, Shuang
Sun, Tao
Meng, Jing
Yang, Cheng
author_facet Yang, Wendong
Li, Zhongwei
Qin, Rong
Wang, Xiaorui
An, Huihui
Wang, Yule
Zhu, Yan
Liu, Yantao
Cai, Shijiao
Chen, Shuang
Sun, Tao
Meng, Jing
Yang, Cheng
author_sort Yang, Wendong
collection PubMed
description Hepatocellular carcinoma (HCC) is a typical hypervascular solid tumor that requires neoangiogenesis for growth. The vascular endothelial growth factor (VEGF) is the most potent proangiogenic factor in neovascularization. The multifunctional Yin-Yang 1 (YY1) is involved in the regulation of tumor malignancy of HCC. However, the relationship between YY1 and endothelial cell-dependent tumor angiogenesis in HCC remains unclear. In this study, we observed that YY1 is positively correlated with microvessel density (MVD) and poor prognosis in HCC tissues. We further found that YY1 promotes the transcriptional activity of VEGFA by binding its promoter in HCC. The secreted VEGFA from HCC cells activates phosphorylation of VEGFR2 to promotes tube formation, cell migration, and invasion of vascular endothelial cells in vitro, and promotes tumor growth and angiogenesis in vivo. In addition, upregulation of YY1 enhanced resistance of bevacizumab in HCC cells. These results indicate that YY1 plays essential roles in HCC angiogenesis and resistance of bevacizumab by inducing VEGFA transcription and that YY1 may represent a potential molecular target for antiangiogenic therapy during HCC progression.
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spelling pubmed-68680522019-12-03 YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA Yang, Wendong Li, Zhongwei Qin, Rong Wang, Xiaorui An, Huihui Wang, Yule Zhu, Yan Liu, Yantao Cai, Shijiao Chen, Shuang Sun, Tao Meng, Jing Yang, Cheng Front Oncol Oncology Hepatocellular carcinoma (HCC) is a typical hypervascular solid tumor that requires neoangiogenesis for growth. The vascular endothelial growth factor (VEGF) is the most potent proangiogenic factor in neovascularization. The multifunctional Yin-Yang 1 (YY1) is involved in the regulation of tumor malignancy of HCC. However, the relationship between YY1 and endothelial cell-dependent tumor angiogenesis in HCC remains unclear. In this study, we observed that YY1 is positively correlated with microvessel density (MVD) and poor prognosis in HCC tissues. We further found that YY1 promotes the transcriptional activity of VEGFA by binding its promoter in HCC. The secreted VEGFA from HCC cells activates phosphorylation of VEGFR2 to promotes tube formation, cell migration, and invasion of vascular endothelial cells in vitro, and promotes tumor growth and angiogenesis in vivo. In addition, upregulation of YY1 enhanced resistance of bevacizumab in HCC cells. These results indicate that YY1 plays essential roles in HCC angiogenesis and resistance of bevacizumab by inducing VEGFA transcription and that YY1 may represent a potential molecular target for antiangiogenic therapy during HCC progression. Frontiers Media S.A. 2019-11-14 /pmc/articles/PMC6868052/ /pubmed/31799179 http://dx.doi.org/10.3389/fonc.2019.01187 Text en Copyright © 2019 Yang, Li, Qin, Wang, An, Wang, Zhu, Liu, Cai, Chen, Sun, Meng and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Yang, Wendong
Li, Zhongwei
Qin, Rong
Wang, Xiaorui
An, Huihui
Wang, Yule
Zhu, Yan
Liu, Yantao
Cai, Shijiao
Chen, Shuang
Sun, Tao
Meng, Jing
Yang, Cheng
YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA
title YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA
title_full YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA
title_fullStr YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA
title_full_unstemmed YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA
title_short YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA
title_sort yy1 promotes endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma by transcriptionally activating vegfa
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868052/
https://www.ncbi.nlm.nih.gov/pubmed/31799179
http://dx.doi.org/10.3389/fonc.2019.01187
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