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

Mu, Wenxin1; Jia, Yiqun2; Chen, Xiaobing1; Li, Haoyu1; Wang, Zhi1; Cheng, Bin1

2020-12-23

10.3389/fcimb.2020.584798

Frontiers in Cellular and Infection Microbiology   影响因子和分区

2235-2988

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.

gingipain cysteine endopeptidases cell cycle cell proliferation colorectal neoplasms Porphyromonas gingivalis

SCI

英语

其他

National Natural Science Foundations of China[81630025,81700979] ; Special Funds for the Cultivation of Guangdong College Students' Scientific and Technological Innovation ("Climbing Program" Special Funds)[pdjh2020a0004]

Immunology ; Microbiology

Immunology ; Microbiology

WOS:000604935900001

FRONTIERS MEDIA SA

Web of Science

1.Sun Yat Sen Univ, Guanghua Sch Stomatol, Hosp Stomatol, Guangdong Prov Key Lab Stomatol, Guangzhou, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Clin Med Coll 2,Affiliated Hosp 1, Stomatol Ctr,Shenzhen Peoples Hosp, Shenzhen, Peoples R China

Mu, Wenxin,Jia, Yiqun,Chen, Xiaobing,et al. Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway[J]. Frontiers in Cellular and Infection Microbiology,2020,10.

Mu, Wenxin,Jia, Yiqun,Chen, Xiaobing,Li, Haoyu,Wang, Zhi,&Cheng, Bin.(2020).Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway.Frontiers in Cellular and Infection Microbiology,10.

Mu, Wenxin,et al."Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway".Frontiers in Cellular and Infection Microbiology 10(2020).