Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance
Toll-like receptor 3 (TLR3) is a member of the TLR family, which has been extensively studied for its antiviral function. It is highly expressed in the endosomes of antigen-presenting immune cells and epithelial cells. TLR3 binds specifically double-strand RNAs (dsRNAs), leading to the activation of...
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MDPI AG
2020-11-01
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Series: | Cancers |
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Online Access: | https://www.mdpi.com/2072-6694/12/11/3227 |
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author | Ximena Maria Muresan Jan Bouchal Zoran Culig Karel Souček |
author_facet | Ximena Maria Muresan Jan Bouchal Zoran Culig Karel Souček |
author_sort | Ximena Maria Muresan |
collection | DOAJ |
description | Toll-like receptor 3 (TLR3) is a member of the TLR family, which has been extensively studied for its antiviral function. It is highly expressed in the endosomes of antigen-presenting immune cells and epithelial cells. TLR3 binds specifically double-strand RNAs (dsRNAs), leading to the activation of mainly two downstream pathways: the phosphorylation of IRF3, with subsequent production of type I interferon, and the activation of NF-κB, which drives the production of inflammatory cytokines and chemokines. Several studies have demonstrated TLR3 expression in multiple neoplasia types including breast, prostate, and lung cancer. Most studies were focused on the beneficial role of TLR3 activation in tumor cells, which leads to the production of cytotoxic cytokines and interferons and promotes caspase-dependent apoptosis. Indeed, ligands of this receptor were proposed for the treatment of cancer, also in combination with conventional chemotherapy. In contrast to these findings, recent evidence showed a link between TLR3 and tumor progression, metastasis, and therapy resistance. In the present review, we summarize the current knowledge of the mechanisms through which TLR3 can either lead to tumor regression or promote carcinogenesis as well as the potential of TLR-based therapies in resistant cancer. |
first_indexed | 2024-03-10T15:09:22Z |
format | Article |
id | doaj.art-c2c88bb503a64538b2db76d2e8e0aff7 |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T15:09:22Z |
publishDate | 2020-11-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
spelling | doaj.art-c2c88bb503a64538b2db76d2e8e0aff72023-11-20T19:28:43ZengMDPI AGCancers2072-66942020-11-011211322710.3390/cancers12113227Toll-Like Receptor 3 in Solid Cancer and Therapy ResistanceXimena Maria Muresan0Jan Bouchal1Zoran Culig2Karel Souček3Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, 612 65 Brno, Czech RepublicDepartment of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital, 779 00 Olomouc, Czech RepublicInternational Clinical Research Center, St. Anne’s University Hospital in Brno, 656 91 Brno, Czech RepublicDepartment of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, 612 65 Brno, Czech RepublicToll-like receptor 3 (TLR3) is a member of the TLR family, which has been extensively studied for its antiviral function. It is highly expressed in the endosomes of antigen-presenting immune cells and epithelial cells. TLR3 binds specifically double-strand RNAs (dsRNAs), leading to the activation of mainly two downstream pathways: the phosphorylation of IRF3, with subsequent production of type I interferon, and the activation of NF-κB, which drives the production of inflammatory cytokines and chemokines. Several studies have demonstrated TLR3 expression in multiple neoplasia types including breast, prostate, and lung cancer. Most studies were focused on the beneficial role of TLR3 activation in tumor cells, which leads to the production of cytotoxic cytokines and interferons and promotes caspase-dependent apoptosis. Indeed, ligands of this receptor were proposed for the treatment of cancer, also in combination with conventional chemotherapy. In contrast to these findings, recent evidence showed a link between TLR3 and tumor progression, metastasis, and therapy resistance. In the present review, we summarize the current knowledge of the mechanisms through which TLR3 can either lead to tumor regression or promote carcinogenesis as well as the potential of TLR-based therapies in resistant cancer.https://www.mdpi.com/2072-6694/12/11/3227toll-like receptor 3therapy resistancecytokinesdsRNAmetastasis |
spellingShingle | Ximena Maria Muresan Jan Bouchal Zoran Culig Karel Souček Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance Cancers toll-like receptor 3 therapy resistance cytokines dsRNA metastasis |
title | Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance |
title_full | Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance |
title_fullStr | Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance |
title_full_unstemmed | Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance |
title_short | Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance |
title_sort | toll like receptor 3 in solid cancer and therapy resistance |
topic | toll-like receptor 3 therapy resistance cytokines dsRNA metastasis |
url | https://www.mdpi.com/2072-6694/12/11/3227 |
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