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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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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. |
format | Online Article Text |
id | pubmed-6868052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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