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FOXO1 inhibits the invasion and metastasis of hepatocellular carcinoma by reversing ZEB2-induced epithelial-mesenchymal transition

The epithelial-to-mesenchymal transition (EMT) program is critical for epithelial cell cancer progression and fibrotic diseases. FOXO1 influences a broad range of physiological and pathological processes. However, the mechanism by which FOXO1 inhibits EMT is not fully understood. In this study, we d...

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Autores principales: Dong, Tianxiu, Zhang, Yu, Chen, Yaodong, Liu, Pengfei, An, Tingting, Zhang, Jiuwei, Yang, Haichao, Zhu, Wenjing, Yang, Xiuhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352090/
https://www.ncbi.nlm.nih.gov/pubmed/27924058
http://dx.doi.org/10.18632/oncotarget.13786
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author Dong, Tianxiu
Zhang, Yu
Chen, Yaodong
Liu, Pengfei
An, Tingting
Zhang, Jiuwei
Yang, Haichao
Zhu, Wenjing
Yang, Xiuhua
author_facet Dong, Tianxiu
Zhang, Yu
Chen, Yaodong
Liu, Pengfei
An, Tingting
Zhang, Jiuwei
Yang, Haichao
Zhu, Wenjing
Yang, Xiuhua
author_sort Dong, Tianxiu
collection PubMed
description The epithelial-to-mesenchymal transition (EMT) program is critical for epithelial cell cancer progression and fibrotic diseases. FOXO1 influences a broad range of physiological and pathological processes. However, the mechanism by which FOXO1 inhibits EMT is not fully understood. In this study, we demonstrated that FOXO1 overexpression inhibited cell motility and invasiveness in vitro and inhibited lung metastasis in vivo. In addition, we found that FOXO1 couldreverse the EMT program. FOXO1 silencing by siRNA in hepatocellular carcinoma (HCC) cell lines enhanced the expression of mesenchymal markers and decreased the expression of the epithelial markers. Consistent with these findings, FOXO1 overexpression exerted opposite effects. Furthermore, we found that FOXO1 levels were inversely correlated with the levels of EMT inducers, including Snail, Slug, ZEB1, ZEB2 and Twist1 in HCC cells. Co-immunoprecipitation and immunohistochemistry assays revealed that an interaction between FOXO1 and ZEB2. A dual-luciferase reporter assay and a ChIP assay further demonstrated that FOXO1 binds to the ZEB2 promoter. Together, these findings suggest that FOXO1 overexpression or ZEB2 inhibition might be potential therapeutic strategies for treating HCC.
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spelling pubmed-53520902017-04-13 FOXO1 inhibits the invasion and metastasis of hepatocellular carcinoma by reversing ZEB2-induced epithelial-mesenchymal transition Dong, Tianxiu Zhang, Yu Chen, Yaodong Liu, Pengfei An, Tingting Zhang, Jiuwei Yang, Haichao Zhu, Wenjing Yang, Xiuhua Oncotarget Research Paper The epithelial-to-mesenchymal transition (EMT) program is critical for epithelial cell cancer progression and fibrotic diseases. FOXO1 influences a broad range of physiological and pathological processes. However, the mechanism by which FOXO1 inhibits EMT is not fully understood. In this study, we demonstrated that FOXO1 overexpression inhibited cell motility and invasiveness in vitro and inhibited lung metastasis in vivo. In addition, we found that FOXO1 couldreverse the EMT program. FOXO1 silencing by siRNA in hepatocellular carcinoma (HCC) cell lines enhanced the expression of mesenchymal markers and decreased the expression of the epithelial markers. Consistent with these findings, FOXO1 overexpression exerted opposite effects. Furthermore, we found that FOXO1 levels were inversely correlated with the levels of EMT inducers, including Snail, Slug, ZEB1, ZEB2 and Twist1 in HCC cells. Co-immunoprecipitation and immunohistochemistry assays revealed that an interaction between FOXO1 and ZEB2. A dual-luciferase reporter assay and a ChIP assay further demonstrated that FOXO1 binds to the ZEB2 promoter. Together, these findings suggest that FOXO1 overexpression or ZEB2 inhibition might be potential therapeutic strategies for treating HCC. Impact Journals LLC 2016-12-03 /pmc/articles/PMC5352090/ /pubmed/27924058 http://dx.doi.org/10.18632/oncotarget.13786 Text en Copyright: © 2017 Dong 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
Dong, Tianxiu
Zhang, Yu
Chen, Yaodong
Liu, Pengfei
An, Tingting
Zhang, Jiuwei
Yang, Haichao
Zhu, Wenjing
Yang, Xiuhua
FOXO1 inhibits the invasion and metastasis of hepatocellular carcinoma by reversing ZEB2-induced epithelial-mesenchymal transition
title FOXO1 inhibits the invasion and metastasis of hepatocellular carcinoma by reversing ZEB2-induced epithelial-mesenchymal transition
title_full FOXO1 inhibits the invasion and metastasis of hepatocellular carcinoma by reversing ZEB2-induced epithelial-mesenchymal transition
title_fullStr FOXO1 inhibits the invasion and metastasis of hepatocellular carcinoma by reversing ZEB2-induced epithelial-mesenchymal transition
title_full_unstemmed FOXO1 inhibits the invasion and metastasis of hepatocellular carcinoma by reversing ZEB2-induced epithelial-mesenchymal transition
title_short FOXO1 inhibits the invasion and metastasis of hepatocellular carcinoma by reversing ZEB2-induced epithelial-mesenchymal transition
title_sort foxo1 inhibits the invasion and metastasis of hepatocellular carcinoma by reversing zeb2-induced epithelial-mesenchymal transition
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352090/
https://www.ncbi.nlm.nih.gov/pubmed/27924058
http://dx.doi.org/10.18632/oncotarget.13786
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