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Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling
Hypervascularity is one of the main characteristics of hepatocellular carcinoma (HCC). However, the mechanisms of angiogenesis in HCC remain controversial. In this study, we investigate the role of Notch1 in angiogenesis of HCC. We found that Notch1 expression was correlated with formation of vascul...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356819/ https://www.ncbi.nlm.nih.gov/pubmed/27705934 http://dx.doi.org/10.18632/oncotarget.12388 |
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author | Jue, Chen Lin, Cui Zhisheng, Zhang Yayun, Qian Feng, Jin Min, Zhao Haibo, Wang Youyang, Shi Hisamitsu, Tadashi Shintaro, Ishikawa Shiyu, Guo Yanqing, Liu |
author_facet | Jue, Chen Lin, Cui Zhisheng, Zhang Yayun, Qian Feng, Jin Min, Zhao Haibo, Wang Youyang, Shi Hisamitsu, Tadashi Shintaro, Ishikawa Shiyu, Guo Yanqing, Liu |
author_sort | Jue, Chen |
collection | PubMed |
description | Hypervascularity is one of the main characteristics of hepatocellular carcinoma (HCC). However, the mechanisms of angiogenesis in HCC remain controversial. In this study, we investigate the role of Notch1 in angiogenesis of HCC. We found that Notch1 expression was correlated with formation of vasculogenic mimicry (VM) and expression of biomarkers of epithelial-to-mesenchymal transition (EMT) in the tumor specimens. Two HCC cell lines, HepG2 and MHCC97-H, with low and high Notch1 expression, respectively, were used to study the mechanism of VM formation both in vitro and in vivo. It was found that MHCC97-H cells, but not HepG2 cells form VM when they grow on matrigel in vitro. HepG2 cells gained the power of forming VM when they were overexpressed with Notch1, while knockdown Notch1 expression in MHCC97-H cells led to the loss of VM forming ability of the cells. Similar results were found in in vivo study. High expression of Notch1 in HepG2 promoted xenograft growth in nude mice, with abundant VM formation in the tumor samples. Moreover, we observed Notch1 was associated with the EMT and malignant behavior of hepatocellular carcinoma by analyzing clinical specimens, models for in vitro and in vivo experiments. HepG2 presented EMT phenomenon when induced by TGF-β1, accompanied by Notch1 activation while MHCC97-H with knockdown of Notch1 lost the responsiveness to TGF-β1 induction. Our results suggest that Notch1 promotes HCC progression through activating EMT pathway and forming VM. Our results will guide targeting Notch1 in new drug development. |
format | Online Article Text |
id | pubmed-5356819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53568192017-04-20 Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling Jue, Chen Lin, Cui Zhisheng, Zhang Yayun, Qian Feng, Jin Min, Zhao Haibo, Wang Youyang, Shi Hisamitsu, Tadashi Shintaro, Ishikawa Shiyu, Guo Yanqing, Liu Oncotarget Research Paper Hypervascularity is one of the main characteristics of hepatocellular carcinoma (HCC). However, the mechanisms of angiogenesis in HCC remain controversial. In this study, we investigate the role of Notch1 in angiogenesis of HCC. We found that Notch1 expression was correlated with formation of vasculogenic mimicry (VM) and expression of biomarkers of epithelial-to-mesenchymal transition (EMT) in the tumor specimens. Two HCC cell lines, HepG2 and MHCC97-H, with low and high Notch1 expression, respectively, were used to study the mechanism of VM formation both in vitro and in vivo. It was found that MHCC97-H cells, but not HepG2 cells form VM when they grow on matrigel in vitro. HepG2 cells gained the power of forming VM when they were overexpressed with Notch1, while knockdown Notch1 expression in MHCC97-H cells led to the loss of VM forming ability of the cells. Similar results were found in in vivo study. High expression of Notch1 in HepG2 promoted xenograft growth in nude mice, with abundant VM formation in the tumor samples. Moreover, we observed Notch1 was associated with the EMT and malignant behavior of hepatocellular carcinoma by analyzing clinical specimens, models for in vitro and in vivo experiments. HepG2 presented EMT phenomenon when induced by TGF-β1, accompanied by Notch1 activation while MHCC97-H with knockdown of Notch1 lost the responsiveness to TGF-β1 induction. Our results suggest that Notch1 promotes HCC progression through activating EMT pathway and forming VM. Our results will guide targeting Notch1 in new drug development. Impact Journals LLC 2016-10-01 /pmc/articles/PMC5356819/ /pubmed/27705934 http://dx.doi.org/10.18632/oncotarget.12388 Text en Copyright: © 2017 Jue et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Jue, Chen Lin, Cui Zhisheng, Zhang Yayun, Qian Feng, Jin Min, Zhao Haibo, Wang Youyang, Shi Hisamitsu, Tadashi Shintaro, Ishikawa Shiyu, Guo Yanqing, Liu Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling |
title | Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling |
title_full | Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling |
title_fullStr | Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling |
title_full_unstemmed | Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling |
title_short | Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling |
title_sort | notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing emt signaling |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356819/ https://www.ncbi.nlm.nih.gov/pubmed/27705934 http://dx.doi.org/10.18632/oncotarget.12388 |
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