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Stimulation of the toll-like receptor 3 promotes metabolic reprogramming in head and neck carcinoma cells
In this study, a possible link between the innate immune recognition receptor TLR3 and metabolic reprogramming in Head and Neck carcinoma (HNC) cells was investigated. The effects of TLR3 stimulation/knock-down were assessed under several culture conditions in 4 HNC cell-lines by cell growth assays,...
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/PMC5347715/ https://www.ncbi.nlm.nih.gov/pubmed/27791989 http://dx.doi.org/10.18632/oncotarget.12892 |
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author | Veyrat, Mathieu Durand, Sylvère Classe, Marion Glavan, Tanja Matijevic Oker, Natalie Kapetanakis, Nikiforos-Ioannis Jiang, Xiaojun Gelin, Aurore Herman, Philippe Casiraghi, Odile Zagzag, David Enot, David Busson, Pierre Vérillaud, Benjamin |
author_facet | Veyrat, Mathieu Durand, Sylvère Classe, Marion Glavan, Tanja Matijevic Oker, Natalie Kapetanakis, Nikiforos-Ioannis Jiang, Xiaojun Gelin, Aurore Herman, Philippe Casiraghi, Odile Zagzag, David Enot, David Busson, Pierre Vérillaud, Benjamin |
author_sort | Veyrat, Mathieu |
collection | PubMed |
description | In this study, a possible link between the innate immune recognition receptor TLR3 and metabolic reprogramming in Head and Neck carcinoma (HNC) cells was investigated. The effects of TLR3 stimulation/knock-down were assessed under several culture conditions in 4 HNC cell-lines by cell growth assays, targeted metabolomics, and glycolysis assays based on time-resolved analysis of proton release (Seahorse analyzer). The stimulation of TLR3 by its synthetic agonist Poly(A:U) resulted in a faster growth of HNC cells under low foetal calf serum conditions. Targeted analysis of glucose metabolism pathways demonstrated a tendency towards a shift from tricarboxylic acid cycle (Krebs cycle) to glycolysis and anabolic reactions in cells treated with Poly(A:U). Glycolysis assays confirmed that TLR3 stimulation enhanced the capacity of malignant cells to switch from oxidative phosphorylation to extra-mitochondrial glycolysis. We found evidence that HIF-1α is involved in this process: addition of the TLR3 agonist resulted in a higher cell concentration of the HIF-1α protein, even in normoxia, whereas knocking-down TLR3 resulted in a lower concentration, even in hypoxia. Finally, we assessed TLR3 expression by immunohistochemistry in a series of 7 HNSCC specimens and found that TLR3 was detected at higher levels in tumors displaying a hypoxic staining pattern. Overall, our results demonstrate that TLR3 stimulation induces the Warburg effect in HNC cells in vitro, and suggest that TLR3 may play a role in tumor adaptation to hypoxia. |
format | Online Article Text |
id | pubmed-5347715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53477152017-03-31 Stimulation of the toll-like receptor 3 promotes metabolic reprogramming in head and neck carcinoma cells Veyrat, Mathieu Durand, Sylvère Classe, Marion Glavan, Tanja Matijevic Oker, Natalie Kapetanakis, Nikiforos-Ioannis Jiang, Xiaojun Gelin, Aurore Herman, Philippe Casiraghi, Odile Zagzag, David Enot, David Busson, Pierre Vérillaud, Benjamin Oncotarget Research Paper In this study, a possible link between the innate immune recognition receptor TLR3 and metabolic reprogramming in Head and Neck carcinoma (HNC) cells was investigated. The effects of TLR3 stimulation/knock-down were assessed under several culture conditions in 4 HNC cell-lines by cell growth assays, targeted metabolomics, and glycolysis assays based on time-resolved analysis of proton release (Seahorse analyzer). The stimulation of TLR3 by its synthetic agonist Poly(A:U) resulted in a faster growth of HNC cells under low foetal calf serum conditions. Targeted analysis of glucose metabolism pathways demonstrated a tendency towards a shift from tricarboxylic acid cycle (Krebs cycle) to glycolysis and anabolic reactions in cells treated with Poly(A:U). Glycolysis assays confirmed that TLR3 stimulation enhanced the capacity of malignant cells to switch from oxidative phosphorylation to extra-mitochondrial glycolysis. We found evidence that HIF-1α is involved in this process: addition of the TLR3 agonist resulted in a higher cell concentration of the HIF-1α protein, even in normoxia, whereas knocking-down TLR3 resulted in a lower concentration, even in hypoxia. Finally, we assessed TLR3 expression by immunohistochemistry in a series of 7 HNSCC specimens and found that TLR3 was detected at higher levels in tumors displaying a hypoxic staining pattern. Overall, our results demonstrate that TLR3 stimulation induces the Warburg effect in HNC cells in vitro, and suggest that TLR3 may play a role in tumor adaptation to hypoxia. Impact Journals LLC 2016-10-25 /pmc/articles/PMC5347715/ /pubmed/27791989 http://dx.doi.org/10.18632/oncotarget.12892 Text en Copyright: © 2016 Veyrat et al. http://creativecommons.org/licenses/by/3.0/ 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 Veyrat, Mathieu Durand, Sylvère Classe, Marion Glavan, Tanja Matijevic Oker, Natalie Kapetanakis, Nikiforos-Ioannis Jiang, Xiaojun Gelin, Aurore Herman, Philippe Casiraghi, Odile Zagzag, David Enot, David Busson, Pierre Vérillaud, Benjamin Stimulation of the toll-like receptor 3 promotes metabolic reprogramming in head and neck carcinoma cells |
title | Stimulation of the toll-like receptor 3 promotes metabolic reprogramming in head and neck carcinoma cells |
title_full | Stimulation of the toll-like receptor 3 promotes metabolic reprogramming in head and neck carcinoma cells |
title_fullStr | Stimulation of the toll-like receptor 3 promotes metabolic reprogramming in head and neck carcinoma cells |
title_full_unstemmed | Stimulation of the toll-like receptor 3 promotes metabolic reprogramming in head and neck carcinoma cells |
title_short | Stimulation of the toll-like receptor 3 promotes metabolic reprogramming in head and neck carcinoma cells |
title_sort | stimulation of the toll-like receptor 3 promotes metabolic reprogramming in head and neck carcinoma cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347715/ https://www.ncbi.nlm.nih.gov/pubmed/27791989 http://dx.doi.org/10.18632/oncotarget.12892 |
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