Porphyromonas gingivalis promotes esophageal squamous cell carcinoma progression and enhances cetuximab resistance via EGFR/GSK3β pathway induced EMT
10.19405/j.cnki.issn1000-1492.2025.10.017
- VernacularTitle:牙龈卟啉单胞菌通过 EGFR/GSK3β 通路诱导 EMT 促进食管鳞癌进展及增强对西妥昔单抗耐药的研究
- Author:
Yaowu Lang
1
;
Pan Chen
1
;
Zichao Zhang
1
;
Ke Liu
1
;
Linlin Shi
1
;
Shegan Gao
1
Author Information
1. Clinical Medical College of Henan University of Science and Technology, The First Afiliated Hospital of Henan University of Science and Technology, Institute of Oncology of Henan University of Science and Technology, Key Laboratory of Microecology and Esophageal Cancer Prevention and Treatment in Henan Province , Key Laboratory of Epigenetics of Tumors in Henan Province , Luoyang 471003
- Publication Type:Journal Article
- Keywords:
Porphyromonas gingivalis;
ESCC;
EGFR;
EMT;
Ctx;
cancer drug resistance
- From:
Acta Universitatis Medicinalis Anhui
2025;60(10):1908-1917
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the regulatory role of Porphyromonas gingivalis(Pg) infection on the EGFR/GSK3β signaling axis, and its impact on epithelial-mesenchymal transition(EMT) and cetuximab(Ctx) resistance in esophageal squamous cell carcinoma(ESCC).
Methods:Single cell RNA sequencing was employed to perform differential analysis of cellular subpopulations, identifying differentially expressed genes in ESCC tissues infected and non-infected with Pg. IHC was conducted to assess the expression of Pg and epidermal growth factor receptor(EGFR) in ESCC tissues. Western blot, RT-PCR, and IF staining were performed to evaluate EGFR expression in Pg infected ESCC cell lines KYSE70 and TE1. ESCC cells were treated with Pg and EGFR inhibitor Ctx, and divided into four groups: control(NC) group, Pg group, Ctx group, Pg+Ctx group. Cell proliferation, migration and invasion abilities were evaluated using CCK-8, plate cloning, wound healing and Transwell assay. Western blot analysis was performed to detect the expression of EMT and EGFR/GSK3β signaling pathway-associated proteins and their phosphorylation levels. Transforming growth factor-β1(TGF-β1) was used to induce EMT in ESCC cells, promoting a transition from the epithelial phenotype to mesenchymal-like phenotype. The differential effects of Ctx on these two phenotypic states were subsequently compared.
Results:Epithelial cells were predominantly enriched in Pg-positive tissues, and Pg infection promoted the upregulation of EGFR expression in ESCC cells. Compared to the NC group, Pg treatment significantly enhanced the proliferation, invasion and migration capabili-ties of ESCC cells, and also increased chemoresistance to Ctx and reduced its antitumor efficacy. Pg induced EMT in ESCC cellsviathe EGFR/GSK3β signaling pathway. Notably, Ctx exhibited markedly weaker inhibitory effects on mesenchymal-like cells compared to epithelial ESCC cells.
Conclusion:Pg promotes ESCC cells proliferation, invasion and migration by regulating EMT through the EGFR/GSK3β signaling pathway, and enhances chemoresistance to Ctx.
- Full text:2026031022402153568牙龈卟啉单胞菌通过EGFR_GSK3β通路诱导EMT促进食管鳞癌进展及增强对西妥昔单抗耐药的研究_郎耀武.pdf
