RANKL promotes migration and invasion of hepatocellular carcinoma cells via NF-κB-mediated epithelial-mesenchymal transition.
<h4>Background</h4>Metastasis accounts for the most deaths in patients with hepatocellular carcinoma (HCC). Receptor activator of nuclear factor kappa B ligand (RANKL) is associated with cancer metastasis, while its role in HCC remains largely unknown.<h4>Methods</h4>Immunohi...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0108507&type=printable |
| _version_ | 1826587327897534464 |
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| author | Fang-Nan Song Meng Duan Long-Zi Liu Zhi-Chao Wang Jie-Yi Shi Liu-Xiao Yang Jian Zhou Jia Fan Qiang Gao Xiao-Ying Wang |
| author_facet | Fang-Nan Song Meng Duan Long-Zi Liu Zhi-Chao Wang Jie-Yi Shi Liu-Xiao Yang Jian Zhou Jia Fan Qiang Gao Xiao-Ying Wang |
| author_sort | Fang-Nan Song |
| collection | DOAJ |
| description | <h4>Background</h4>Metastasis accounts for the most deaths in patients with hepatocellular carcinoma (HCC). Receptor activator of nuclear factor kappa B ligand (RANKL) is associated with cancer metastasis, while its role in HCC remains largely unknown.<h4>Methods</h4>Immunohistochemistry was performed to determine the expression of RANK in HCC tissue (n = 398). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to examine the expression of RANK, E-cadherin, N-cadherin, vimentin, Snail, Slug, Twist and MMPs in HCC cells. Wound healing and Transwell assays were used to evaluate cell migration and invasion ability.<h4>Results</h4>We found that expression of RANK, the receptor of RANKL, was significantly higher in HCC tumor tissues than in peritumor liver tissues (p<0.001). Constitutive expression of RANK was detected in HCC cell lines, which can be up-regulated when HCC cells were stimulated with RANKL. Notably, in vitro experiments showed that activation of RANKL-RANK axis significantly promoted migration and invasion ability of HCC cells. In addition, RANKL stimulation increased the expression levels of N-cadherin, Snail, and Twist, while decreased the expression of E-cadherin, with concomitant activation of NF-κB signaling pathway. Moreover, administration of the NF-κB inhibitor attenuated RANKL-induced migration, invasion and epithelial-mesenchymal transition of HCC cells.<h4>Conclusions</h4>RANKL could potentiate migration and invasion ability of RANK-positive HCC cells through NF-κB pathway-mediated epithelial-mesenchymal transition, which means that RANKL-RANK axis could be a potential target for HCC therapy. |
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| id | doaj.art-fb22b85191044f309ce9b3eb2fa0fc3d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T16:23:41Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-fb22b85191044f309ce9b3eb2fa0fc3d2025-02-22T05:32:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10850710.1371/journal.pone.0108507RANKL promotes migration and invasion of hepatocellular carcinoma cells via NF-κB-mediated epithelial-mesenchymal transition.Fang-Nan SongMeng DuanLong-Zi LiuZhi-Chao WangJie-Yi ShiLiu-Xiao YangJian ZhouJia FanQiang GaoXiao-Ying Wang<h4>Background</h4>Metastasis accounts for the most deaths in patients with hepatocellular carcinoma (HCC). Receptor activator of nuclear factor kappa B ligand (RANKL) is associated with cancer metastasis, while its role in HCC remains largely unknown.<h4>Methods</h4>Immunohistochemistry was performed to determine the expression of RANK in HCC tissue (n = 398). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to examine the expression of RANK, E-cadherin, N-cadherin, vimentin, Snail, Slug, Twist and MMPs in HCC cells. Wound healing and Transwell assays were used to evaluate cell migration and invasion ability.<h4>Results</h4>We found that expression of RANK, the receptor of RANKL, was significantly higher in HCC tumor tissues than in peritumor liver tissues (p<0.001). Constitutive expression of RANK was detected in HCC cell lines, which can be up-regulated when HCC cells were stimulated with RANKL. Notably, in vitro experiments showed that activation of RANKL-RANK axis significantly promoted migration and invasion ability of HCC cells. In addition, RANKL stimulation increased the expression levels of N-cadherin, Snail, and Twist, while decreased the expression of E-cadherin, with concomitant activation of NF-κB signaling pathway. Moreover, administration of the NF-κB inhibitor attenuated RANKL-induced migration, invasion and epithelial-mesenchymal transition of HCC cells.<h4>Conclusions</h4>RANKL could potentiate migration and invasion ability of RANK-positive HCC cells through NF-κB pathway-mediated epithelial-mesenchymal transition, which means that RANKL-RANK axis could be a potential target for HCC therapy.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0108507&type=printable |
| spellingShingle | Fang-Nan Song Meng Duan Long-Zi Liu Zhi-Chao Wang Jie-Yi Shi Liu-Xiao Yang Jian Zhou Jia Fan Qiang Gao Xiao-Ying Wang RANKL promotes migration and invasion of hepatocellular carcinoma cells via NF-κB-mediated epithelial-mesenchymal transition. PLoS ONE |
| title | RANKL promotes migration and invasion of hepatocellular carcinoma cells via NF-κB-mediated epithelial-mesenchymal transition. |
| title_full | RANKL promotes migration and invasion of hepatocellular carcinoma cells via NF-κB-mediated epithelial-mesenchymal transition. |
| title_fullStr | RANKL promotes migration and invasion of hepatocellular carcinoma cells via NF-κB-mediated epithelial-mesenchymal transition. |
| title_full_unstemmed | RANKL promotes migration and invasion of hepatocellular carcinoma cells via NF-κB-mediated epithelial-mesenchymal transition. |
| title_short | RANKL promotes migration and invasion of hepatocellular carcinoma cells via NF-κB-mediated epithelial-mesenchymal transition. |
| title_sort | rankl promotes migration and invasion of hepatocellular carcinoma cells via nf κb mediated epithelial mesenchymal transition |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0108507&type=printable |
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