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Upregulation of PD-L1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells
BACKGROUND: The epithelial-to-mesenchymal transition (EMT) status is associated with programmed death-1 ligand 1 (PD-L1) expression in various cancers. However, the role and molecular mechanism of PD-L1 in the EMT of sorafenib-resistant hepatocellular carcinoma (HCC) cells remain elusive. In this st...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603871/ https://www.ncbi.nlm.nih.gov/pubmed/33163195 http://dx.doi.org/10.1093/gastro/goaa049 |
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author | Xu, Gui-Li Ni, Cai-Fang Liang, Han-Si Xu, Yun-Hua Wang, Wan-Sheng Shen, Jian Li, Ming-Ming Zhu, Xiao-Li |
author_facet | Xu, Gui-Li Ni, Cai-Fang Liang, Han-Si Xu, Yun-Hua Wang, Wan-Sheng Shen, Jian Li, Ming-Ming Zhu, Xiao-Li |
author_sort | Xu, Gui-Li |
collection | PubMed |
description | BACKGROUND: The epithelial-to-mesenchymal transition (EMT) status is associated with programmed death-1 ligand 1 (PD-L1) expression in various cancers. However, the role and molecular mechanism of PD-L1 in the EMT of sorafenib-resistant hepatocellular carcinoma (HCC) cells remain elusive. In this study, we aimed to investigate the regulation of PD-L1 on the EMT in sorafenib-resistant HCC cells. METHODS: Initially, the sorafenib-resistant HCC cell lines HepG2 SR and Huh7 SR were established. Western-blot assays were used to detect the expression of PD-L1, E-cadherin, and N-cadherin. The intervention and overexpression of PD-L1 were used to explore the role of PD-L1 in the regulation of EMT in HepG2 SR and Huh7 SR cells. Cell migration and invasion were assessed by transwell assays. PD-L1 or Sterol regulatory element-binding protein 1 (SREBP-1) overexpression and knock-down were performed in order to study the mechanism of PD-L1 in sorafenib-resistant HCC cells. RESULTS: PD-L1 expression was upregulated, whereas E-cadherin levels were downregulated and N-cadherin expression was increased in HepG2 SR and Huh7 SR cells. The cell viabilities of HepG2 and Huh7 cells were lower than those of HepG2 SR and Huh7 SR cells. PD-L1 overexpression reduced E-cadherin expression and increased N-cadherin levels, whereas PD-L1 knock-down increased E-cadherin expression and decreased N-cadherin expression. PD-L1 expression promoted EMT and the migratory and invasive abilities of HepG2 SR and Huh7 SR cells. PD-L1 promoted the EMT of sorafenib-resistant HCC cells via the PI3K/Akt pathway by activating SREBP-1 expression in HepG2 SR and Huh7 SR cells. CONCLUSIONS: The findings reveal that PD-L1 expression promotes EMT of sorafenib-resistant HCC cells. |
format | Online Article Text |
id | pubmed-7603871 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-76038712020-11-06 Upregulation of PD-L1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells Xu, Gui-Li Ni, Cai-Fang Liang, Han-Si Xu, Yun-Hua Wang, Wan-Sheng Shen, Jian Li, Ming-Ming Zhu, Xiao-Li Gastroenterol Rep (Oxf) Original Articles BACKGROUND: The epithelial-to-mesenchymal transition (EMT) status is associated with programmed death-1 ligand 1 (PD-L1) expression in various cancers. However, the role and molecular mechanism of PD-L1 in the EMT of sorafenib-resistant hepatocellular carcinoma (HCC) cells remain elusive. In this study, we aimed to investigate the regulation of PD-L1 on the EMT in sorafenib-resistant HCC cells. METHODS: Initially, the sorafenib-resistant HCC cell lines HepG2 SR and Huh7 SR were established. Western-blot assays were used to detect the expression of PD-L1, E-cadherin, and N-cadherin. The intervention and overexpression of PD-L1 were used to explore the role of PD-L1 in the regulation of EMT in HepG2 SR and Huh7 SR cells. Cell migration and invasion were assessed by transwell assays. PD-L1 or Sterol regulatory element-binding protein 1 (SREBP-1) overexpression and knock-down were performed in order to study the mechanism of PD-L1 in sorafenib-resistant HCC cells. RESULTS: PD-L1 expression was upregulated, whereas E-cadherin levels were downregulated and N-cadherin expression was increased in HepG2 SR and Huh7 SR cells. The cell viabilities of HepG2 and Huh7 cells were lower than those of HepG2 SR and Huh7 SR cells. PD-L1 overexpression reduced E-cadherin expression and increased N-cadherin levels, whereas PD-L1 knock-down increased E-cadherin expression and decreased N-cadherin expression. PD-L1 expression promoted EMT and the migratory and invasive abilities of HepG2 SR and Huh7 SR cells. PD-L1 promoted the EMT of sorafenib-resistant HCC cells via the PI3K/Akt pathway by activating SREBP-1 expression in HepG2 SR and Huh7 SR cells. CONCLUSIONS: The findings reveal that PD-L1 expression promotes EMT of sorafenib-resistant HCC cells. Oxford University Press 2020-09-10 /pmc/articles/PMC7603871/ /pubmed/33163195 http://dx.doi.org/10.1093/gastro/goaa049 Text en © The Author(s) 2020. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Articles Xu, Gui-Li Ni, Cai-Fang Liang, Han-Si Xu, Yun-Hua Wang, Wan-Sheng Shen, Jian Li, Ming-Ming Zhu, Xiao-Li Upregulation of PD-L1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells |
title | Upregulation of PD-L1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells |
title_full | Upregulation of PD-L1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells |
title_fullStr | Upregulation of PD-L1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells |
title_full_unstemmed | Upregulation of PD-L1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells |
title_short | Upregulation of PD-L1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells |
title_sort | upregulation of pd-l1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603871/ https://www.ncbi.nlm.nih.gov/pubmed/33163195 http://dx.doi.org/10.1093/gastro/goaa049 |
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