Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance
Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic
Document type Journal Article, Review
Grant support
17-28518A
Agentura Pro Zdravotnický Výzkum České Republiky
LQ1605
Ministerstvo Školství, Mládeže a Tělovýchovy
ENOCH No. CZ.02.1.01/0.0/0.0/16_019/0000868
Ministerstvo Školství, Mládeže a Tělovýchovy
PubMed
33147700
PubMed Central
PMC7692054
DOI
10.3390/cancers12113227
PII: cancers12113227
Knihovny.cz E-resources
- Keywords
- cytokines, dsRNA, metastasis, therapy resistance, toll-like receptor 3,
- Publication type
- Journal Article MeSH
- Review MeSH
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.
Department of Experimental Biology Faculty of Science Masaryk University 625 00 Brno Czech Republic
Department of Urology Experimental Urology Innsbruck Medical University A 6020 Innsbruck Austria
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