Hepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the Notch pathway

Abstract Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1β has been reported to be associated with risk for a variety of cancers. The purpose of this study is to investigate whether the expression of...

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Autores principales:	Jing-Ni Zhu, Lu Jiang, Jing-Hua Jiang, Xue Yang, Xiao-Yong Li, Jian-Xin Zeng, Rong-Yu Shi, Yang Shi, Xiao-Rong Pan, Zhi-Peng Han, Li-Xin Wei
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/627233bcdea94e5ea8eba5a1d42f27ee
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spelling	oai:doaj.org-article:627233bcdea94e5ea8eba5a1d42f27ee2021-12-02T11:40:43ZHepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the Notch pathway10.1038/s41598-017-04116-72045-2322https://doaj.org/article/627233bcdea94e5ea8eba5a1d42f27ee2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04116-7https://doaj.org/toc/2045-2322Abstract Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1β has been reported to be associated with risk for a variety of cancers. The purpose of this study is to investigate whether the expression of HNF-1β promotes the malignancy of HCC and its mechanism. We retrospectively investigated the expression of HNF-1β in 90 patients with hepatocellular carcinoma and found that the high expression of HNF-1β indicated poor prognosis. We overexpressed HNF-1β in liver cancer cell lines and found the expression of liver progenitor cell markers and stemness were upregulated. The invasion ability and epithelial-mesenchymal transition (EMT)-associated genes were also significantly higher in liver cancer cells overexpressing HNF-1β than in the control group. A mechanistic study suggested the activation of the Notch signalling pathway probably plays a key role downstream of HNF-1β. More importantly, HNF-1β promoted tumourigenesis of HCC cells in vivo. In conclusion, high expression of HNF-1β not only promoted the de-differentiation of HCC cells into liver cancer stem cells through activating the Notch pathway but also enhanced the invasive potential of HCC cells and EMT occurrence, which would contribute to the enhancement of cell migration and invasion.Jing-Ni ZhuLu JiangJing-Hua JiangXue YangXiao-Yong LiJian-Xin ZengRong-Yu ShiYang ShiXiao-Rong PanZhi-Peng HanLi-Xin WeiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jing-Ni Zhu Lu Jiang Jing-Hua Jiang Xue Yang Xiao-Yong Li Jian-Xin Zeng Rong-Yu Shi Yang Shi Xiao-Rong Pan Zhi-Peng Han Li-Xin Wei Hepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the Notch pathway
description	Abstract Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1β has been reported to be associated with risk for a variety of cancers. The purpose of this study is to investigate whether the expression of HNF-1β promotes the malignancy of HCC and its mechanism. We retrospectively investigated the expression of HNF-1β in 90 patients with hepatocellular carcinoma and found that the high expression of HNF-1β indicated poor prognosis. We overexpressed HNF-1β in liver cancer cell lines and found the expression of liver progenitor cell markers and stemness were upregulated. The invasion ability and epithelial-mesenchymal transition (EMT)-associated genes were also significantly higher in liver cancer cells overexpressing HNF-1β than in the control group. A mechanistic study suggested the activation of the Notch signalling pathway probably plays a key role downstream of HNF-1β. More importantly, HNF-1β promoted tumourigenesis of HCC cells in vivo. In conclusion, high expression of HNF-1β not only promoted the de-differentiation of HCC cells into liver cancer stem cells through activating the Notch pathway but also enhanced the invasive potential of HCC cells and EMT occurrence, which would contribute to the enhancement of cell migration and invasion.
format	article
author	Jing-Ni Zhu Lu Jiang Jing-Hua Jiang Xue Yang Xiao-Yong Li Jian-Xin Zeng Rong-Yu Shi Yang Shi Xiao-Rong Pan Zhi-Peng Han Li-Xin Wei
author_facet	Jing-Ni Zhu Lu Jiang Jing-Hua Jiang Xue Yang Xiao-Yong Li Jian-Xin Zeng Rong-Yu Shi Yang Shi Xiao-Rong Pan Zhi-Peng Han Li-Xin Wei
author_sort	Jing-Ni Zhu
title	Hepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the Notch pathway
title_short	Hepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the Notch pathway
title_full	Hepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the Notch pathway
title_fullStr	Hepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the Notch pathway
title_full_unstemmed	Hepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the Notch pathway
title_sort	hepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the notch pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/627233bcdea94e5ea8eba5a1d42f27ee
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Hepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the Notch pathway

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