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Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway

Porphyromonas gingivalis (P. gingivalis) is a keystone pathogen in periodontitis. However, several clinical studies have revealed an enrichment of P. gingivalis in the stool samples and colorectal mucosa of colorectal cancer patients. Thus, the goal of this study was to determine whether P. gingival...

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Autores principales: Mu, Wenxin, Jia, Yiqun, Chen, Xiaobing, Li, Haoyu, Wang, Zhi, Cheng, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785964/
https://www.ncbi.nlm.nih.gov/pubmed/33425779
http://dx.doi.org/10.3389/fcimb.2020.584798
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author Mu, Wenxin
Jia, Yiqun
Chen, Xiaobing
Li, Haoyu
Wang, Zhi
Cheng, Bin
author_facet Mu, Wenxin
Jia, Yiqun
Chen, Xiaobing
Li, Haoyu
Wang, Zhi
Cheng, Bin
author_sort Mu, Wenxin
collection PubMed
description Porphyromonas gingivalis (P. gingivalis) is a keystone pathogen in periodontitis. However, several clinical studies have revealed an enrichment of P. gingivalis in the stool samples and colorectal mucosa of colorectal cancer patients. Thus, the goal of this study was to determine whether P. gingivalis can promote colorectal cancer progression in vitro. We established an acute infection model (24 h, multiplicity of infection =100) of P. gingivalis invasion of colorectal cancer cells to study the alterations induced by P. gingivalis in the proliferation and cell cycle of colorectal cancer cells. We observed that P. gingivalis can adhere and invade host cells a few hours after infection. Once invaded, P. gingivalis significantly promoted colorectal cancer cell proliferation, and the percentage of S phase cells was increased in the cell cycle assay. However, KDP136, a gingipain-deficient mutant of P. gingivalis 33277, showed a decreased ability to promote colorectal cancer cell proliferation, indicating that gingipain is associated with colorectal cancer cell proliferation. Furthermore, we extracted RNA from colorectal cancer cells for high-throughput sequencing analysis and reconfirmed the results by quantitative polymerase chain reaction and western blot analyses. The results suggested that the MAPK/ERK signaling pathway is significantly activated by P. gingivalis, while these changes were not observed for KDP136. In conclusion, P. gingivalis can invade cells and promote the proliferation of colorectal cancer cells by activating the MAPK/ERK signaling pathway. Gingipain is an essential virulence factor in this interaction.
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spelling pubmed-77859642021-01-07 Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway Mu, Wenxin Jia, Yiqun Chen, Xiaobing Li, Haoyu Wang, Zhi Cheng, Bin Front Cell Infect Microbiol Cellular and Infection Microbiology Porphyromonas gingivalis (P. gingivalis) is a keystone pathogen in periodontitis. However, several clinical studies have revealed an enrichment of P. gingivalis in the stool samples and colorectal mucosa of colorectal cancer patients. Thus, the goal of this study was to determine whether P. gingivalis can promote colorectal cancer progression in vitro. We established an acute infection model (24 h, multiplicity of infection =100) of P. gingivalis invasion of colorectal cancer cells to study the alterations induced by P. gingivalis in the proliferation and cell cycle of colorectal cancer cells. We observed that P. gingivalis can adhere and invade host cells a few hours after infection. Once invaded, P. gingivalis significantly promoted colorectal cancer cell proliferation, and the percentage of S phase cells was increased in the cell cycle assay. However, KDP136, a gingipain-deficient mutant of P. gingivalis 33277, showed a decreased ability to promote colorectal cancer cell proliferation, indicating that gingipain is associated with colorectal cancer cell proliferation. Furthermore, we extracted RNA from colorectal cancer cells for high-throughput sequencing analysis and reconfirmed the results by quantitative polymerase chain reaction and western blot analyses. The results suggested that the MAPK/ERK signaling pathway is significantly activated by P. gingivalis, while these changes were not observed for KDP136. In conclusion, P. gingivalis can invade cells and promote the proliferation of colorectal cancer cells by activating the MAPK/ERK signaling pathway. Gingipain is an essential virulence factor in this interaction. Frontiers Media S.A. 2020-12-23 /pmc/articles/PMC7785964/ /pubmed/33425779 http://dx.doi.org/10.3389/fcimb.2020.584798 Text en Copyright © 2020 Mu, Jia, Chen, Li, Wang and Cheng 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 Cellular and Infection Microbiology
Mu, Wenxin
Jia, Yiqun
Chen, Xiaobing
Li, Haoyu
Wang, Zhi
Cheng, Bin
Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway
title Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway
title_full Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway
title_fullStr Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway
title_full_unstemmed Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway
title_short Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway
title_sort intracellular porphyromonas gingivalis promotes the proliferation of colorectal cancer cells via the mapk/erk signaling pathway
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785964/
https://www.ncbi.nlm.nih.gov/pubmed/33425779
http://dx.doi.org/10.3389/fcimb.2020.584798
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