Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway.
Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway.
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细胞内牙龈卟啉单胞菌通过 MAPK/ERK 信号通路促进结直肠癌细胞增殖。
DOI：
10.3389/fcimb.2020.584798
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发表时间：
2020
影响因子：
5.7
通讯作者：
Cheng B
中科院分区：
文献类型：
--
作者：
Mu W;Jia Y;Chen X;Li H;Wang Z;Cheng B
牙龈卟啉单胞菌（Porphyromonasgingivalis，P. gingivalis）是牙周炎的重要致病菌。然而，一些临床研究已经揭示了牙龈卟啉单胞菌在结直肠癌患者的粪便样品和结直肠粘膜中的富集。因此，本研究的目的是确定牙龈卟啉单胞菌是否可以在体外促进结直肠癌的进展。我们建立了牙龈卟啉单胞菌侵袭结直肠癌细胞的急性感染模型（24 h，感染复数=100），以研究牙龈卟啉单胞菌诱导结直肠癌细胞增殖和细胞周期的变化。我们观察到牙龈卟啉单胞菌在感染后数小时即可粘附并侵入宿主细胞。牙龈卟啉单胞菌侵入大肠癌细胞后，可显著促进大肠癌细胞增殖，细胞周期分析显示S期细胞比例增加。然而，牙龈卟啉单胞菌33277的牙龈卟啉菌蛋白酶缺陷突变体KDP 136显示出促进结直肠癌细胞增殖的能力降低，表明牙龈卟啉菌蛋白酶与结直肠癌细胞增殖相关。此外，我们从结直肠癌细胞中提取RNA进行高通量测序分析，并通过定量聚合酶链反应和蛋白质印迹分析再次确认结果。结果表明，牙龈卟啉单胞菌显著激活MAPK/ERK信号通路，而KDP 136没有观察到这些变化。结论牙龈卟啉单胞菌可通过激活MAPK/ERK信号通路侵入大肠癌细胞，促进大肠癌细胞增殖。在这种相互作用中，牙龈蛋白酶是一种重要的毒力因子。
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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影响因子：
24.5
作者：
Michaud DS;Izard J;Wilhelm-Benartzi CS;You DH;Grote VA;Tjønneland A;Dahm CC;Overvad K;Jenab M;Fedirko V;Boutron-Ruault MC;Clavel-Chapelon F;Racine A;Kaaks R;Boeing H;Foerster J;Trichopoulou A;Lagiou P;Trichopoulos D;Sacerdote C;Sieri S;Palli D;Tumino R;Panico S;Siersema PD;Peeters PH;Lund E;Barricarte A;Huerta JM;Molina-Montes E;Dorronsoro M;Quirós JR;Duell EJ;Ye W;Sund M;Lindkvist B;Johansen D;Khaw KT;Wareham N;Travis RC;Vineis P;Bueno-de-Mesquita HB;Riboli E
通讯作者：
Riboli E
影响因子：
3.7
作者：
Gao S;Li S;Ma Z;Liang S;Shan T;Zhang M;Zhu X;Zhang P;Liu G;Zhou F;Yuan X;Jia R;Potempa J;Scott DA;Lamont RJ;Wang H;Feng X
通讯作者：
Feng X
影响因子：
3.7
作者：
Chen W;Liu F;Ling Z;Tong X;Xiang C
通讯作者：
Xiang C
影响因子：
5.2
作者：
Lee K;Roberts JS;Choi CH;Atanasova KR;Yilmaz Ö
通讯作者：
Yilmaz Ö
影响因子：
3.4
作者：
Belton, CM;Izutsu, KT;Lamont, RJ
通讯作者：
Lamont, RJ