{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:16:38Z","timestamp":1788315398958,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Emerging evidence suggests that oral pathogens may contribute to the development of systemic malignancies.\n \n Porphyromonas gingivalis<\/jats:italic>\n <\/jats:styled-content>\n (Pg), a major periodontal pathogen, has been implicated in several cancers including esophageal squamous cell carcinoma (ESCC). However, the molecular mechanisms underlying this association remain unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n This study aimed to investigate the impact of\n \n Porphyromonas gingivalis<\/jats:italic>\n <\/jats:styled-content>\n (Pg) on the growth of esophageal squamous cell carcinoma (\n ESCC<\/jats:styled-content>\n ) and its potential mechanisms.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n THP\u20101 cells were differentiated into M0 macrophages with PMA and divided into control group, Pg group, and Pg\u2009+\u2009siATR group. THP\u20101 cells were divided into three groups: control group, Pg group, and Pg\u2009+\u2009siATR group. The control and Pg groups were transfected with siNC, while the Pg\u2009+\u2009siATR group was transfected with siATR. After transfection, the Pg group and Pg\u2009+\u2009siATR group were incubated with 200 MOI pg. The control group was cultured normally. Cells and supernatants were collected, and macrophage polarization status was detected with qRT\u2010PCR, Western blot, and flow cytometry. Macrophages treated differently were co\u2010cultured with human esophageal squamous cell carcinoma cell line KYSE150. The proliferation, invasion, and apoptosis of KYSE150 were examined. KYSE150+shATR and KYSE150+shNC cell lines were constructed with a lentivirus system. Thirty male BALB\/c mice aged 6\u20138\u2009weeks were randomly divided into control group, pg group, and pg+shATR group, with 10 mice in each group. For the Pg and Pg+shATR groups, 200\u2009\u03bcL Pg (1\u2009\u00d7\u200910\n 7<\/jats:sup>\n \u2009CFU\/mouse) was applied to the mandibular molars of mice four times a week for 1\u2009month. The control group was treated with the vehicle (CMC) only. After 3\u2009weeks of bacterial colonization, KYSE150+shATR cells (1\u2009\u00d7\u200910\n 6<\/jats:sup>\n \u2009cells\/mouse) were inoculated into the right axilla of mice in the Pg+shATR group, while KYSE150\u2009+\u2009shNC (1\u2009\u00d7\u200910\n 6<\/jats:sup>\n \u2009cells\/mouse) were inoculated into the right axilla of mice in the control and Pg groups. Tumor volume was measured with calipers every 7\u2009days. After 4\u2009weeks of experimentation, D\u2010luciferin potassium salt was injected intraperitoneally at 150\u2009mg\/kg, and bioluminescence imaging was performed after sodium pentobarbital anesthesia. The mice were euthanized post\u2010imaging, and macrophage polarization in tumor tissues was examined with qRT\u2010PCR, histopathological examination, and Western blot.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n In this study, we found that Pg could promote the polarization of M0 macrophages into M2 macrophages, while also promoting the malignant progression of KYSE150 cells. The expression levels of ATR, phosphorylated ATR (p\u2010ATR), and M2 macrophage markers (CD206, Arg1, and VEGF) decreased when ATR was inhibited. In BALB\/c mice, Pg\u2010induced ATR activation promoted the growth of subcutaneously implanted tumors by recruiting M2\u2010type TAMs. Experimental data also indicated an association between M2 polarization, decreased p\u2010chik, and ATR.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This study reveals that Pg can activate the ataxia\u2010telangiectasia and Rad3\u2010related protein (ATR) signaling pathway, inducing the polarization of M2 tumor\u2010associated macrophages (TAM), thereby promoting the growth of ESCC. This provides a new theoretical basis for the prevention and treatment of ESCC.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jop.70157","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:41:28Z","timestamp":1780641688000},"page":"917-925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pg<\/scp>\n \u2010Induced\n ATR<\/scp>\n Activation Promotes\n ESCC<\/scp>\n Progression via\n M2 TAM<\/scp>\n Polarization"],"prefix":"10.1111","volume":"55","author":[{"given":"Yanhua","family":"Sun","sequence":"first","affiliation":[{"name":"Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases Hubei Minzu University Enshi Hubei China"},{"name":"Medical Department Hubei Minzu University Enshi Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases Hubei Minzu University Enshi Hubei China"},{"name":"Department of Thoracic Surgery Minda Hospital of Hubei Minzu University Enshi Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1875-9082","authenticated-orcid":false,"given":"Xiaodong","family":"Wei","sequence":"additional","affiliation":[{"name":"Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases Hubei Minzu University Enshi Hubei China"},{"name":"Department of Thoracic Surgery Minda Hospital of Hubei Minzu University Enshi Hubei 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