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TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin
Metastasis is one of the main contributors to the poor prognosis of hepatocellular carcinoma (HCC). However, the underlying mechanism of HCC metastasis remains largely unknown. Here, we showed that TXNDC12, a thioredoxin-like protein, was upregulated in highly metastatic HCC cell lines as well as in...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206186/ https://www.ncbi.nlm.nih.gov/pubmed/31570854 http://dx.doi.org/10.1038/s41418-019-0421-7 |
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author | Yuan, Kefei Xie, Kunlin Lan, Tian Xu, Lin Chen, Xiangzheng Li, Xuefeng Liao, Mingheng Li, Jiaxin Huang, Jiwei Zeng, Yong Wu, Hong |
author_facet | Yuan, Kefei Xie, Kunlin Lan, Tian Xu, Lin Chen, Xiangzheng Li, Xuefeng Liao, Mingheng Li, Jiaxin Huang, Jiwei Zeng, Yong Wu, Hong |
author_sort | Yuan, Kefei |
collection | PubMed |
description | Metastasis is one of the main contributors to the poor prognosis of hepatocellular carcinoma (HCC). However, the underlying mechanism of HCC metastasis remains largely unknown. Here, we showed that TXNDC12, a thioredoxin-like protein, was upregulated in highly metastatic HCC cell lines as well as in portal vein tumor thrombus and lung metastasis tissues of HCC patients. We found that the enforced expression of TXNDC12 promoted metastasis both in vitro and in vivo. Subsequent mechanistic investigations revealed that TXNDC12 promoted metastasis through upregulation of the ZEB1-mediated epithelial–mesenchymal transition (EMT) process. We subsequently showed that TXNDC12 overexpression stimulated the nuclear translocation and activation of β-catenin, a positive transcriptional regulator of ZEB1. Accordingly, we found that TXNDC12 interacted with β-catenin and that the thioredoxin-like domain of TXNDC12 was essential for the interaction between TXNDC12 and β-catenin as well as for TXNDC12-mediated β-catenin activation. Moreover, high levels of TXNDC12 in clinical HCC tissues correlated with elevated nuclear β-catenin levels and predicted worse overall and disease-free survival. In summary, our study demonstrated that TXNDC12 could activate β-catenin via protein–protein interaction and promote ZEB1-mediated EMT and HCC metastasis. |
format | Online Article Text |
id | pubmed-7206186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72061862020-05-08 TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin Yuan, Kefei Xie, Kunlin Lan, Tian Xu, Lin Chen, Xiangzheng Li, Xuefeng Liao, Mingheng Li, Jiaxin Huang, Jiwei Zeng, Yong Wu, Hong Cell Death Differ Article Metastasis is one of the main contributors to the poor prognosis of hepatocellular carcinoma (HCC). However, the underlying mechanism of HCC metastasis remains largely unknown. Here, we showed that TXNDC12, a thioredoxin-like protein, was upregulated in highly metastatic HCC cell lines as well as in portal vein tumor thrombus and lung metastasis tissues of HCC patients. We found that the enforced expression of TXNDC12 promoted metastasis both in vitro and in vivo. Subsequent mechanistic investigations revealed that TXNDC12 promoted metastasis through upregulation of the ZEB1-mediated epithelial–mesenchymal transition (EMT) process. We subsequently showed that TXNDC12 overexpression stimulated the nuclear translocation and activation of β-catenin, a positive transcriptional regulator of ZEB1. Accordingly, we found that TXNDC12 interacted with β-catenin and that the thioredoxin-like domain of TXNDC12 was essential for the interaction between TXNDC12 and β-catenin as well as for TXNDC12-mediated β-catenin activation. Moreover, high levels of TXNDC12 in clinical HCC tissues correlated with elevated nuclear β-catenin levels and predicted worse overall and disease-free survival. In summary, our study demonstrated that TXNDC12 could activate β-catenin via protein–protein interaction and promote ZEB1-mediated EMT and HCC metastasis. Nature Publishing Group UK 2019-09-30 2020-04 /pmc/articles/PMC7206186/ /pubmed/31570854 http://dx.doi.org/10.1038/s41418-019-0421-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Yuan, Kefei Xie, Kunlin Lan, Tian Xu, Lin Chen, Xiangzheng Li, Xuefeng Liao, Mingheng Li, Jiaxin Huang, Jiwei Zeng, Yong Wu, Hong TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin |
title | TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin |
title_full | TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin |
title_fullStr | TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin |
title_full_unstemmed | TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin |
title_short | TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin |
title_sort | txndc12 promotes emt and metastasis of hepatocellular carcinoma cells via activation of β-catenin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206186/ https://www.ncbi.nlm.nih.gov/pubmed/31570854 http://dx.doi.org/10.1038/s41418-019-0421-7 |
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