Critical roles of p53 in epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most malignant tumors and the biggest obstacle in curing HCC is its high metastasis potential. Alteration of p53 is the most frequent genetic change found in HCC. Although the biological function of p53 in tumor initiation and progression has been well ch...

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Autores principales:	Zheng Wang, Yuhui Jiang, Dongxian Guan, Jingjing Li, Hongkun Yin, Yi Pan, Dong Xie, Yan Chen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6cbb550d2cc149ab8387282859b18b4a
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spelling	oai:doaj.org-article:6cbb550d2cc149ab8387282859b18b4a2021-11-18T08:57:24ZCritical roles of p53 in epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma cells.1932-620310.1371/journal.pone.0072846https://doaj.org/article/6cbb550d2cc149ab8387282859b18b4a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24023784/?tool=EBIhttps://doaj.org/toc/1932-6203Hepatocellular carcinoma (HCC) is one of the most malignant tumors and the biggest obstacle in curing HCC is its high metastasis potential. Alteration of p53 is the most frequent genetic change found in HCC. Although the biological function of p53 in tumor initiation and progression has been well characterized, whether or not p53 is implicated in metastasis of HCC is largely unknown. In this study, we analyzed the potential functions of p53 in epithelial-mesenchymal transition (EMT) and metastasis of HCC cells. Both insulin- and TGF-β1-induced changes of critical EMT markers were greatly enhanced by p53 knockdown in HCC cells. The insulin- and TGF-β1-stimulated migration of HCC cells were enhanced by p53 knockdown. Furthermore, in vivo metastasis of HCC cells using different mouse models was robustly enhanced by p53 knockdown. In addition, we found that p53 regulation on EMT and metastasis involves β-catenin signaling. The nuclear accumulation and transcriptional activity of β-catenin was modulated by p53. The enhanced EMT phenotype, cell migration and tumor metastasis of HCC cells by p53 knockdown were abrogated by inhibiting β-catenin signal pathway. In conclusion, this study reveals that p53 plays a pivotal role in EMT and metastasis of HCC cells via its regulation on β-catenin signaling.Zheng WangYuhui JiangDongxian GuanJingjing LiHongkun YinYi PanDong XieYan ChenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e72846 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zheng Wang Yuhui Jiang Dongxian Guan Jingjing Li Hongkun Yin Yi Pan Dong Xie Yan Chen Critical roles of p53 in epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma cells.
description	Hepatocellular carcinoma (HCC) is one of the most malignant tumors and the biggest obstacle in curing HCC is its high metastasis potential. Alteration of p53 is the most frequent genetic change found in HCC. Although the biological function of p53 in tumor initiation and progression has been well characterized, whether or not p53 is implicated in metastasis of HCC is largely unknown. In this study, we analyzed the potential functions of p53 in epithelial-mesenchymal transition (EMT) and metastasis of HCC cells. Both insulin- and TGF-β1-induced changes of critical EMT markers were greatly enhanced by p53 knockdown in HCC cells. The insulin- and TGF-β1-stimulated migration of HCC cells were enhanced by p53 knockdown. Furthermore, in vivo metastasis of HCC cells using different mouse models was robustly enhanced by p53 knockdown. In addition, we found that p53 regulation on EMT and metastasis involves β-catenin signaling. The nuclear accumulation and transcriptional activity of β-catenin was modulated by p53. The enhanced EMT phenotype, cell migration and tumor metastasis of HCC cells by p53 knockdown were abrogated by inhibiting β-catenin signal pathway. In conclusion, this study reveals that p53 plays a pivotal role in EMT and metastasis of HCC cells via its regulation on β-catenin signaling.
format	article
author	Zheng Wang Yuhui Jiang Dongxian Guan Jingjing Li Hongkun Yin Yi Pan Dong Xie Yan Chen
author_facet	Zheng Wang Yuhui Jiang Dongxian Guan Jingjing Li Hongkun Yin Yi Pan Dong Xie Yan Chen
author_sort	Zheng Wang
title	Critical roles of p53 in epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma cells.
title_short	Critical roles of p53 in epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma cells.
title_full	Critical roles of p53 in epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma cells.
title_fullStr	Critical roles of p53 in epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma cells.
title_full_unstemmed	Critical roles of p53 in epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma cells.
title_sort	critical roles of p53 in epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6cbb550d2cc149ab8387282859b18b4a
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Critical roles of p53 in epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma cells.

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