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Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1
Immunogenic cell death (ICD) of tumor cells occurs via various pathways that activate immune cell systems against cancer. Previous studies have demonstrated that shikonin (SK), a plant secondary metabolite, can confer strong pharmacological activities that activate ICD and strong immunogenicity of t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190049/ https://www.ncbi.nlm.nih.gov/pubmed/27248319 http://dx.doi.org/10.18632/oncotarget.9660 |
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author | Yin, Shu-Yi Efferth, Thomas Jian, Feng-Yin Chen, Yung-Hsiang Liu, Chia-I Wang, Andrew H.J. Chen, Yet-Ran Hsiao, Pei-Wen Yang, Ning-Sun |
author_facet | Yin, Shu-Yi Efferth, Thomas Jian, Feng-Yin Chen, Yung-Hsiang Liu, Chia-I Wang, Andrew H.J. Chen, Yet-Ran Hsiao, Pei-Wen Yang, Ning-Sun |
author_sort | Yin, Shu-Yi |
collection | PubMed |
description | Immunogenic cell death (ICD) of tumor cells occurs via various pathways that activate immune cell systems against cancer. Previous studies have demonstrated that shikonin (SK), a plant secondary metabolite, can confer strong pharmacological activities that activate ICD and strong immunogenicity of tumor cells. However, the exact hierarchical regulatory mechanisms including the molecular targets of SK-activated immunogenicity are still unknown. Here, the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was revealed to serve as a specific protein target for SK. This binding plays a key role in SK-stimulated ICD activity and the suppression of post-transcriptional mRNA processing, including nuclear export activity of newly synthesized mRNAs in mammary carcinoma cells in vitro. Moreover, it also mechanistically mediates the anti-metastatic effect of a tumor cell lysate (TCL) vaccine, which can be readily generated from SK-treated 4T1 tumor cells (SK-TCL), and the derived tumor-immunogenicity of SK-TCL-treated dendritic cells in vivo. Together, the identification of hnRNPA1 as the intracellular molecular target provides compelling pharmacology-based knowledge for the potential clinical use of SK-induced immunogenicity. In addition, SK may also serve as a potent suppressor that interferes with specific post-transcriptional activities, a mechanism which may be useful for exploitation in cancer therapeutics. |
format | Online Article Text |
id | pubmed-5190049 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-51900492017-01-05 Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1 Yin, Shu-Yi Efferth, Thomas Jian, Feng-Yin Chen, Yung-Hsiang Liu, Chia-I Wang, Andrew H.J. Chen, Yet-Ran Hsiao, Pei-Wen Yang, Ning-Sun Oncotarget Research Paper Immunogenic cell death (ICD) of tumor cells occurs via various pathways that activate immune cell systems against cancer. Previous studies have demonstrated that shikonin (SK), a plant secondary metabolite, can confer strong pharmacological activities that activate ICD and strong immunogenicity of tumor cells. However, the exact hierarchical regulatory mechanisms including the molecular targets of SK-activated immunogenicity are still unknown. Here, the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was revealed to serve as a specific protein target for SK. This binding plays a key role in SK-stimulated ICD activity and the suppression of post-transcriptional mRNA processing, including nuclear export activity of newly synthesized mRNAs in mammary carcinoma cells in vitro. Moreover, it also mechanistically mediates the anti-metastatic effect of a tumor cell lysate (TCL) vaccine, which can be readily generated from SK-treated 4T1 tumor cells (SK-TCL), and the derived tumor-immunogenicity of SK-TCL-treated dendritic cells in vivo. Together, the identification of hnRNPA1 as the intracellular molecular target provides compelling pharmacology-based knowledge for the potential clinical use of SK-induced immunogenicity. In addition, SK may also serve as a potent suppressor that interferes with specific post-transcriptional activities, a mechanism which may be useful for exploitation in cancer therapeutics. Impact Journals LLC 2016-05-27 /pmc/articles/PMC5190049/ /pubmed/27248319 http://dx.doi.org/10.18632/oncotarget.9660 Text en Copyright: © 2016 Yin et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Yin, Shu-Yi Efferth, Thomas Jian, Feng-Yin Chen, Yung-Hsiang Liu, Chia-I Wang, Andrew H.J. Chen, Yet-Ran Hsiao, Pei-Wen Yang, Ning-Sun Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1 |
title | Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1 |
title_full | Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1 |
title_fullStr | Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1 |
title_full_unstemmed | Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1 |
title_short | Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1 |
title_sort | immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnrnpa1 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190049/ https://www.ncbi.nlm.nih.gov/pubmed/27248319 http://dx.doi.org/10.18632/oncotarget.9660 |
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