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Tspan5 promotes epithelial–mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating Notch signalling
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide due to a high rate of tumour metastasis and disease recurrence. In physiological conditions, tetraspanins interact with specific partner proteins in tetraspanin‐enriched microdomains and regulate their subcellular localizatio...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564648/ https://www.ncbi.nlm.nih.gov/pubmed/33955149 http://dx.doi.org/10.1002/1878-0261.12980 |
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author | Xie, Qian Guo, Huiling He, Peirong Deng, Huan Gao, Yanjun Dong, Ningning Niu, Wenbo Liu, Tiancai Li, Ming Wang, Suihai Wu, Yingsong Li, Ji‐Liang |
author_facet | Xie, Qian Guo, Huiling He, Peirong Deng, Huan Gao, Yanjun Dong, Ningning Niu, Wenbo Liu, Tiancai Li, Ming Wang, Suihai Wu, Yingsong Li, Ji‐Liang |
author_sort | Xie, Qian |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide due to a high rate of tumour metastasis and disease recurrence. In physiological conditions, tetraspanins interact with specific partner proteins in tetraspanin‐enriched microdomains and regulate their subcellular localization and function. However, the function of Tspan5 in pathological processes, particularly in cancer biology and its clinical significance, are still unclear. Here, we describe that a high expression of Tspan5 is significantly associated with some clinicopathological features including invasive length, vascular invasion, clinical stage and poor overall survival of HCC patients. Alterations of Tspan5 expression by lentivirus transductions in HCC cells demonstrated that Tspan5 promotes wound healing and cell migration in vitro and tumour metastasis of HCC cells in vivo. Mechanistic studies revealed that Tspan5 promoted cell migration and tumour metastasis by increasing the enzymatic maturation of ADAM10 and activating Notch signalling via the increase of the cleavage of the Notch1 receptor catalysed by the γ‐secretase complex. Activation of Notch signalling by Tspan5 was shown further to enhance the epithelial–mesenchymal transition (EMT) and actin skeleton rearrangement of tumour cells. In clinical HCC samples, Tspan5 expression is strongly correlated with many key molecules acting in Notch signalling and EMT, highlighting the role of Tspan5 in the regulation of Notch signalling, EMT and tumour metastasis of HCC. Our findings provide new insights into the mechanism of tumour metastasis and disease progression of HCC and may facilitate the development of novel clinical intervention strategies against HCC. |
format | Online Article Text |
id | pubmed-8564648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85646482021-11-09 Tspan5 promotes epithelial–mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating Notch signalling Xie, Qian Guo, Huiling He, Peirong Deng, Huan Gao, Yanjun Dong, Ningning Niu, Wenbo Liu, Tiancai Li, Ming Wang, Suihai Wu, Yingsong Li, Ji‐Liang Mol Oncol Research Articles Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide due to a high rate of tumour metastasis and disease recurrence. In physiological conditions, tetraspanins interact with specific partner proteins in tetraspanin‐enriched microdomains and regulate their subcellular localization and function. However, the function of Tspan5 in pathological processes, particularly in cancer biology and its clinical significance, are still unclear. Here, we describe that a high expression of Tspan5 is significantly associated with some clinicopathological features including invasive length, vascular invasion, clinical stage and poor overall survival of HCC patients. Alterations of Tspan5 expression by lentivirus transductions in HCC cells demonstrated that Tspan5 promotes wound healing and cell migration in vitro and tumour metastasis of HCC cells in vivo. Mechanistic studies revealed that Tspan5 promoted cell migration and tumour metastasis by increasing the enzymatic maturation of ADAM10 and activating Notch signalling via the increase of the cleavage of the Notch1 receptor catalysed by the γ‐secretase complex. Activation of Notch signalling by Tspan5 was shown further to enhance the epithelial–mesenchymal transition (EMT) and actin skeleton rearrangement of tumour cells. In clinical HCC samples, Tspan5 expression is strongly correlated with many key molecules acting in Notch signalling and EMT, highlighting the role of Tspan5 in the regulation of Notch signalling, EMT and tumour metastasis of HCC. Our findings provide new insights into the mechanism of tumour metastasis and disease progression of HCC and may facilitate the development of novel clinical intervention strategies against HCC. John Wiley and Sons Inc. 2021-07-27 2021-11 /pmc/articles/PMC8564648/ /pubmed/33955149 http://dx.doi.org/10.1002/1878-0261.12980 Text en © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Xie, Qian Guo, Huiling He, Peirong Deng, Huan Gao, Yanjun Dong, Ningning Niu, Wenbo Liu, Tiancai Li, Ming Wang, Suihai Wu, Yingsong Li, Ji‐Liang Tspan5 promotes epithelial–mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating Notch signalling |
title | Tspan5 promotes epithelial–mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating Notch signalling |
title_full | Tspan5 promotes epithelial–mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating Notch signalling |
title_fullStr | Tspan5 promotes epithelial–mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating Notch signalling |
title_full_unstemmed | Tspan5 promotes epithelial–mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating Notch signalling |
title_short | Tspan5 promotes epithelial–mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating Notch signalling |
title_sort | tspan5 promotes epithelial–mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating notch signalling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564648/ https://www.ncbi.nlm.nih.gov/pubmed/33955149 http://dx.doi.org/10.1002/1878-0261.12980 |
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