Cargando…
Human Cancer Cells Sense Cytosolic Nucleic Acids Through the RIG-I–MAVS Pathway and cGAS–STING Pathway
Pattern recognition receptors (PRRs) are germline-encoded host sensors of the innate immune system. Some human cancer cells have been reported to express PRRs. However, nucleic acid sensors in human cancers have not been studied in detail. Therefore, we systematically analyzed the expression, molecu...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820189/ https://www.ncbi.nlm.nih.gov/pubmed/33490069 http://dx.doi.org/10.3389/fcell.2020.606001 |
_version_ | 1783639154879365120 |
---|---|
author | Qiao, Yuan Zhu, Shan Deng, Shuanglin Zou, Shan-Shan Gao, Bao Zang, Guoxia Wu, Jing Jiang, Yuxue Liu, Yong-Jun Chen, Jingtao |
author_facet | Qiao, Yuan Zhu, Shan Deng, Shuanglin Zou, Shan-Shan Gao, Bao Zang, Guoxia Wu, Jing Jiang, Yuxue Liu, Yong-Jun Chen, Jingtao |
author_sort | Qiao, Yuan |
collection | PubMed |
description | Pattern recognition receptors (PRRs) are germline-encoded host sensors of the innate immune system. Some human cancer cells have been reported to express PRRs. However, nucleic acid sensors in human cancers have not been studied in detail. Therefore, we systematically analyzed the expression, molecular cascade, and functions of TLR3, RIG-I, MDA5, LGP2, cGAS, and STING in human cancer cells. TLR3, TRIF, RIG-I, MDA5, LGP2, and MAVS were expressed in 22 cell lines. The majority of cell lines responded to only RIG-I ligands 5′-ppp-dsRNA, Poly(I:C)-HMW, Poly(I:C)-LMW, and/or Poly(dA:dT), as revealed by IRF3 phosphorylation and IFN-β secretion. IFN-β secretion was inhibited by RIG-I and MAVS knockdown. cGAS and STING were co-expressed in 10 of 22 cell lines, but IFN-β secretion was not induced by STING ligands ISD, HSV60, VACV70, Poly(dG:dC), and 3′3′-cGAMP in cGAS and STING intact cell lines. Further experiments revealed that the cGAS–STING pathway was activated, as revealed by TBK1 and IRF3 phosphorylation and IFN-β and ISG mRNA expression. These results suggest that human epithelial cancer cells respond to cytosolic RNA through the RIG-I–MAVS pathway but only sense cytosolic DNA through the cGAS–STING pathway. These findings are relevant for cancer immunotherapy approaches based on targeting nucleic acid receptors. |
format | Online Article Text |
id | pubmed-7820189 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78201892021-01-23 Human Cancer Cells Sense Cytosolic Nucleic Acids Through the RIG-I–MAVS Pathway and cGAS–STING Pathway Qiao, Yuan Zhu, Shan Deng, Shuanglin Zou, Shan-Shan Gao, Bao Zang, Guoxia Wu, Jing Jiang, Yuxue Liu, Yong-Jun Chen, Jingtao Front Cell Dev Biol Cell and Developmental Biology Pattern recognition receptors (PRRs) are germline-encoded host sensors of the innate immune system. Some human cancer cells have been reported to express PRRs. However, nucleic acid sensors in human cancers have not been studied in detail. Therefore, we systematically analyzed the expression, molecular cascade, and functions of TLR3, RIG-I, MDA5, LGP2, cGAS, and STING in human cancer cells. TLR3, TRIF, RIG-I, MDA5, LGP2, and MAVS were expressed in 22 cell lines. The majority of cell lines responded to only RIG-I ligands 5′-ppp-dsRNA, Poly(I:C)-HMW, Poly(I:C)-LMW, and/or Poly(dA:dT), as revealed by IRF3 phosphorylation and IFN-β secretion. IFN-β secretion was inhibited by RIG-I and MAVS knockdown. cGAS and STING were co-expressed in 10 of 22 cell lines, but IFN-β secretion was not induced by STING ligands ISD, HSV60, VACV70, Poly(dG:dC), and 3′3′-cGAMP in cGAS and STING intact cell lines. Further experiments revealed that the cGAS–STING pathway was activated, as revealed by TBK1 and IRF3 phosphorylation and IFN-β and ISG mRNA expression. These results suggest that human epithelial cancer cells respond to cytosolic RNA through the RIG-I–MAVS pathway but only sense cytosolic DNA through the cGAS–STING pathway. These findings are relevant for cancer immunotherapy approaches based on targeting nucleic acid receptors. Frontiers Media S.A. 2021-01-08 /pmc/articles/PMC7820189/ /pubmed/33490069 http://dx.doi.org/10.3389/fcell.2020.606001 Text en Copyright © 2021 Qiao, Zhu, Deng, Zou, Gao, Zang, Wu, Jiang, Liu and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Qiao, Yuan Zhu, Shan Deng, Shuanglin Zou, Shan-Shan Gao, Bao Zang, Guoxia Wu, Jing Jiang, Yuxue Liu, Yong-Jun Chen, Jingtao Human Cancer Cells Sense Cytosolic Nucleic Acids Through the RIG-I–MAVS Pathway and cGAS–STING Pathway |
title | Human Cancer Cells Sense Cytosolic Nucleic Acids Through the RIG-I–MAVS Pathway and cGAS–STING Pathway |
title_full | Human Cancer Cells Sense Cytosolic Nucleic Acids Through the RIG-I–MAVS Pathway and cGAS–STING Pathway |
title_fullStr | Human Cancer Cells Sense Cytosolic Nucleic Acids Through the RIG-I–MAVS Pathway and cGAS–STING Pathway |
title_full_unstemmed | Human Cancer Cells Sense Cytosolic Nucleic Acids Through the RIG-I–MAVS Pathway and cGAS–STING Pathway |
title_short | Human Cancer Cells Sense Cytosolic Nucleic Acids Through the RIG-I–MAVS Pathway and cGAS–STING Pathway |
title_sort | human cancer cells sense cytosolic nucleic acids through the rig-i–mavs pathway and cgas–sting pathway |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820189/ https://www.ncbi.nlm.nih.gov/pubmed/33490069 http://dx.doi.org/10.3389/fcell.2020.606001 |
work_keys_str_mv | AT qiaoyuan humancancercellssensecytosolicnucleicacidsthroughtherigimavspathwayandcgasstingpathway AT zhushan humancancercellssensecytosolicnucleicacidsthroughtherigimavspathwayandcgasstingpathway AT dengshuanglin humancancercellssensecytosolicnucleicacidsthroughtherigimavspathwayandcgasstingpathway AT zoushanshan humancancercellssensecytosolicnucleicacidsthroughtherigimavspathwayandcgasstingpathway AT gaobao humancancercellssensecytosolicnucleicacidsthroughtherigimavspathwayandcgasstingpathway AT zangguoxia humancancercellssensecytosolicnucleicacidsthroughtherigimavspathwayandcgasstingpathway AT wujing humancancercellssensecytosolicnucleicacidsthroughtherigimavspathwayandcgasstingpathway AT jiangyuxue humancancercellssensecytosolicnucleicacidsthroughtherigimavspathwayandcgasstingpathway AT liuyongjun humancancercellssensecytosolicnucleicacidsthroughtherigimavspathwayandcgasstingpathway AT chenjingtao humancancercellssensecytosolicnucleicacidsthroughtherigimavspathwayandcgasstingpathway |