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Interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma
Autophagy has an important role in tumor biology of hepatocellular carcinoma (HCC). Recent studies demonstrated that tissue factor (TF) combined with coagulation factor VII (FVII) has a pathological role by activating a G-protein-coupled receptor called protease-activated receptor 2 (PAR2) for tumor...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047908/ https://www.ncbi.nlm.nih.gov/pubmed/24853422 http://dx.doi.org/10.1038/cddis.2014.212 |
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author | Chen, K-D Wang, C-C Tsai, M-C Wu, C-H Yang, H-J Chen, L-Y Nakano, T Goto, S Huang, K-T Hu, T-H Chen, C-L Lin, C-C |
author_facet | Chen, K-D Wang, C-C Tsai, M-C Wu, C-H Yang, H-J Chen, L-Y Nakano, T Goto, S Huang, K-T Hu, T-H Chen, C-L Lin, C-C |
author_sort | Chen, K-D |
collection | PubMed |
description | Autophagy has an important role in tumor biology of hepatocellular carcinoma (HCC). Recent studies demonstrated that tissue factor (TF) combined with coagulation factor VII (FVII) has a pathological role by activating a G-protein-coupled receptor called protease-activated receptor 2 (PAR2) for tumor growth. The present study aimed to investigate the interactions of autophagy and the coagulation cascade in HCC. Seventy HCC patients who underwent curative liver resection were recruited. Immunohistochemical staining and western blotting were performed to determine TF, FVII, PAR2 and light chain 3 (LC3A/B) expressions in tumors and their contiguous normal regions. We found that the levels of autophagic marker LC3A/B-II and coagulation proteins (TF, FVII and PAR2) were inversely correlated in human HCC tissues. Treatments with TF, FVII or PAR2 agonist downregulated LC3A/B-II with an increased level of mTOR in Hep3B cells; in contrast, knockdown of TF, FVII or PAR2 increased LC3A/B. Furthermore, mTOR silencing restored the impaired expression of LC3A/B-II in TF-, FVII- or PAR2-treated Hep3B cells and activated autophagy. Last, as an in vivo correlate, we administered TF, FVII or PAR2 agonist in a NOD/severe combined immunodeficiency xenograft model and showed decreased LC3A/B protein levels in HepG2 tumors with treatments. Overall, our present study demonstrated that TF, FVII and PAR2 regulated autophagy mainly via mTOR signaling. The interaction of coagulation and autophagic pathways may provide potential targets for further therapeutic application in HCC. |
format | Online Article Text |
id | pubmed-4047908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-40479082014-06-12 Interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma Chen, K-D Wang, C-C Tsai, M-C Wu, C-H Yang, H-J Chen, L-Y Nakano, T Goto, S Huang, K-T Hu, T-H Chen, C-L Lin, C-C Cell Death Dis Original Article Autophagy has an important role in tumor biology of hepatocellular carcinoma (HCC). Recent studies demonstrated that tissue factor (TF) combined with coagulation factor VII (FVII) has a pathological role by activating a G-protein-coupled receptor called protease-activated receptor 2 (PAR2) for tumor growth. The present study aimed to investigate the interactions of autophagy and the coagulation cascade in HCC. Seventy HCC patients who underwent curative liver resection were recruited. Immunohistochemical staining and western blotting were performed to determine TF, FVII, PAR2 and light chain 3 (LC3A/B) expressions in tumors and their contiguous normal regions. We found that the levels of autophagic marker LC3A/B-II and coagulation proteins (TF, FVII and PAR2) were inversely correlated in human HCC tissues. Treatments with TF, FVII or PAR2 agonist downregulated LC3A/B-II with an increased level of mTOR in Hep3B cells; in contrast, knockdown of TF, FVII or PAR2 increased LC3A/B. Furthermore, mTOR silencing restored the impaired expression of LC3A/B-II in TF-, FVII- or PAR2-treated Hep3B cells and activated autophagy. Last, as an in vivo correlate, we administered TF, FVII or PAR2 agonist in a NOD/severe combined immunodeficiency xenograft model and showed decreased LC3A/B protein levels in HepG2 tumors with treatments. Overall, our present study demonstrated that TF, FVII and PAR2 regulated autophagy mainly via mTOR signaling. The interaction of coagulation and autophagic pathways may provide potential targets for further therapeutic application in HCC. Nature Publishing Group 2014-05 2014-05-22 /pmc/articles/PMC4047908/ /pubmed/24853422 http://dx.doi.org/10.1038/cddis.2014.212 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Chen, K-D Wang, C-C Tsai, M-C Wu, C-H Yang, H-J Chen, L-Y Nakano, T Goto, S Huang, K-T Hu, T-H Chen, C-L Lin, C-C Interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma |
title | Interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma |
title_full | Interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma |
title_fullStr | Interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma |
title_full_unstemmed | Interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma |
title_short | Interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma |
title_sort | interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047908/ https://www.ncbi.nlm.nih.gov/pubmed/24853422 http://dx.doi.org/10.1038/cddis.2014.212 |
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