Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC- -dependent mechanism
Abstract
Toll-like receptors (TLRs) are known to play a key role in the innate immune system particularly in inflammatory response against invading pathogens. Recent reports strongly indicate that they play important roles in cancer cells. Prostate cancer represents one of the most common cancer for which no cure is available once metastatic and androgen refractory. Since TLR3 has been recently suggested as a possible therapeutic target in some cancer cell lines, we studied TLR3 expression and functionality in two human prostate cancer cell lines, LNCaP and PC3. We report that both cell lines express TLR3 and that the TLR3 agonist poly (I:C) activates mitogen-activated protein kinases and induces inhibition of proliferation as well as caspase-dependent apoptosis. By using pharmacological and genetic approaches, we demonstrate the involvement of TLR3 in poly (I:C)-induced effects. We also show that a novel interferon-independent pathway involving protein kinase C (PKC)-alpha activation, upstream of p38 and c-jun N-terminal kinase, is responsible for poly (I:C) pro-apoptotic effects on LNCaP cells. To our knowledge, this is the first report describing a role of PKC-alpha in poly (I:C)-mediated apoptosis. The comprehension of the mechanisms underlying TLR3-mediated apoptosis can contribute tools to develop new agonists useful for the treatment of prostate cancer.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
TLR3 can directly trigger apoptosis in human cancer cells in response to poly(I:C).
“TLR3 can directly trigger apoptosis in human cancer cells in response to the double-strand RNA synthetic agonist polyinosinic-polycytidylic acid (poly(I:C)) [28, 29], which is a mimic for viral double-stranded RNA that triggers an innate immune response following viral infection.”
From Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells (2016) · cites this paper as [28]
Poly(I:C) treatment induced TLR3 dependent apoptosis in human prostate cancer cells.
“Paone et al., [28] showed that poly(I:C) treatment induced TLR3 dependent apoptosis in human prostate cancer cells.”
From Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells (2016) · cites this paper as [28]
Cites
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129 · see citing works
Innate immune recognition of viral infection
Kawai, T., & Akira, S. (2006) · Nature Immunology · doi:10.1038/ni1303 · Cited by 1,899 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Matsumoto, M., Tatematsu, M., Nishikawa, F., Azuma, M., Ishii, N., Morii-Sakai, A., Shime, H., & Seya, T. (2015) · Nature Communications · doi:10.1038/ncomms7280 · Cited by 130 · see citing works
Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells
Menendez, D., Lowe, J. M., Snipe, J., & Resnick, M. A. (2016) · Oncotarget · doi:10.18632/oncotarget.11210 · Cited by 31 · see citing works
- Authors
- Paone, A., Starace, D., Galli, R., Padula, F., De Cesaris, P., Filippini, A., Ziparo, E., & Riccioli, A.
- Affiliations
- Istituto Pasteur (IT)
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-05-29
- Volume
- 29
- Issue
- 7
- Pages
- 1334-1342
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2125840697
- Cited by
- 160
- References
- 2
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 10 · 2020: 9 · 2019: 10 · 2018: 4 · 2017: 10 · 2016: 5 · 2015: 11 · 2014: 10 · 2013: 18 · 2012: 19
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- TLR3, prostate cancer, apoptosis, protein kinase C alpha, poly(I:C), p38 MAPK, c-Jun N-terminal kinase, caspase-dependent apoptosis, LNCaP cells, PC-3 cells, TLR3 agonist, cancer immunotherapy
- MeSH terms
- Enzyme Activation, Humans, Male, Phosphorylation, Poly I-C, Prostatic Neoplasms, Receptors, Androgen, Transfection, Tumor Suppressor Protein p53, Interferon-beta, Apoptosis, Mitogen-Activated Protein Kinases, Cell Line, Tumor, p38 Mitogen-Activated Protein Kinases, MAP Kinase Kinase 4, Cell Growth Processes, Toll-Like Receptor 3, Protein Kinase C-alpha
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
