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TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line

Human Papillomavirus is responsible for a wide range of mucosal lesions and tumors. The immune system participate in tumorigenesis in different ways. For example, signaling pathways triggered by Toll-like receptors (TLR) play a role in chemotherapy resistance in several tumor types and are candidate...

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Autores principales: Morale, Mirian Galliote, Tamura, Rodrigo Esaki, Cintra, Ricardo, Araújo, Natália Meneses, Villa, Luisa Lina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039070/
https://www.ncbi.nlm.nih.gov/pubmed/35468924
http://dx.doi.org/10.1038/s41598-022-09980-6
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author Morale, Mirian Galliote
Tamura, Rodrigo Esaki
Cintra, Ricardo
Araújo, Natália Meneses
Villa, Luisa Lina
author_facet Morale, Mirian Galliote
Tamura, Rodrigo Esaki
Cintra, Ricardo
Araújo, Natália Meneses
Villa, Luisa Lina
author_sort Morale, Mirian Galliote
collection PubMed
description Human Papillomavirus is responsible for a wide range of mucosal lesions and tumors. The immune system participate in tumorigenesis in different ways. For example, signaling pathways triggered by Toll-like receptors (TLR) play a role in chemotherapy resistance in several tumor types and are candidates for contributing to the development of HPV-induced tumors. Here, we studied the receptor TLR4 and the adaptor molecule SARM1 in HeLa cells, an HPV-positive cervical cancer cell line. Knocking out of these genes individually proved to be important for maintaining cell viability and proliferation. TLR4 knock out cells were more sensitive to cisplatin treatment, which was illustrated by an increased frequency of apoptotic cells. Furthermore, TLR4 and SARM1 modulated ROS production, which was induced by cell death in response to cisplatin. In conclusion, TLR4 and SARM1 are important for therapy resistance and cervical cancer cell viability and may be relevant clinical targets.
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spelling pubmed-90390702022-04-27 TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line Morale, Mirian Galliote Tamura, Rodrigo Esaki Cintra, Ricardo Araújo, Natália Meneses Villa, Luisa Lina Sci Rep Article Human Papillomavirus is responsible for a wide range of mucosal lesions and tumors. The immune system participate in tumorigenesis in different ways. For example, signaling pathways triggered by Toll-like receptors (TLR) play a role in chemotherapy resistance in several tumor types and are candidates for contributing to the development of HPV-induced tumors. Here, we studied the receptor TLR4 and the adaptor molecule SARM1 in HeLa cells, an HPV-positive cervical cancer cell line. Knocking out of these genes individually proved to be important for maintaining cell viability and proliferation. TLR4 knock out cells were more sensitive to cisplatin treatment, which was illustrated by an increased frequency of apoptotic cells. Furthermore, TLR4 and SARM1 modulated ROS production, which was induced by cell death in response to cisplatin. In conclusion, TLR4 and SARM1 are important for therapy resistance and cervical cancer cell viability and may be relevant clinical targets. Nature Publishing Group UK 2022-04-25 /pmc/articles/PMC9039070/ /pubmed/35468924 http://dx.doi.org/10.1038/s41598-022-09980-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Morale, Mirian Galliote
Tamura, Rodrigo Esaki
Cintra, Ricardo
Araújo, Natália Meneses
Villa, Luisa Lina
TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line
title TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line
title_full TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line
title_fullStr TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line
title_full_unstemmed TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line
title_short TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line
title_sort tlr4 and sarm1 modulate survival and chemoresistance in an hpv-positive cervical cancer cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039070/
https://www.ncbi.nlm.nih.gov/pubmed/35468924
http://dx.doi.org/10.1038/s41598-022-09980-6
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