中国肿瘤生物治疗杂志2024，Vol.31Issue(8)：769-776,8.DOI:10.3872/j.issn.1007-385x.2024.08.004
牙龈卟啉单胞菌通过GARP促进TGF-β/SMAD轴介导食管鳞状细胞癌细胞的上皮间质转化
Porphyromonas gingivalis promotes epithelial-mesenchymal transition of esophageal squamous cell carcinoma cells mediated by TGF-β/SMAD signaling via GARP
摘要
Abstract
Objective:To elucidate the molecular mechanism by which Porphyromonas gingivalis(Pg)induces epithelial-mesenchymal transition(EMT)in esophageal squamous cell carcinoma(ESCC)cells.Methods:KEGG was used to identify the biological pathways enriched by Pg-induced differentially expressed genes in ESCC.WB and/or immunofluorescence(IF)were used to detect the changes in the expression of glycoprotein-A repetitions predominant protein(GARP),TGF-β,pSMAD/SMAD,Snail,Oct4 and EMT-related molecules in Pg-induced ESCC cells.ELISA was used to measure changes in TGF-β1 level.Immunohistochemistry was used to detect the expression of GARP and TGF-β1 in ESCC tissues.The tumorigenic effect of Pg on ESCC was verified by Transwell assays and animal experiments.Results:Pg activated multiple signaling pathways,such as TGF-β,Hippo,and PI3K/Akt.Pg-infection stimulated an increased secretion of total TGF-β1 and active TFG-β1 in ESCC cells(P<0.01),leading to SMAD2/3 phosphorylation and nuclear translocation,which induced increased protein expression of N-cadherin,Snail,and Oct4 and decreased E-cadherin.These alterations collectively promoted the migration and invasion of ESCC cells and the growth of subcutaneous tumor in nude mice(all P<0.01).Silencing GARP expression in ESCC cells reversed the phenotypic changes induced by Pg.The protein levels of TGF-β1 and GARP in ESCC tissues with high Pg abundance were higher than those in ESCC tissues with low Pg abundance.The abundance of Pg was positively correlated with the protein expression of TGF-β1 and GARP(P=0.001 5).Conclusion:Pg activates the TGF-β/Smad axis through GARP to promote the occurrence of EMT in ESCC cells,thereby facilitating the migration,invasion and growth of ESCC cells.Pg clearance or TGF-β signaling blockade can reverse these Pg-induced promotive effects on ESCC.关键词
食管鳞状细胞癌/牙龈卟啉单胞菌/糖蛋白A重复优势蛋白/TGF-β/SMAD/上皮间质转化Key words
esophageal squamous cell carcinoma(ESCC)/Porphyromonas gingivalis(Pg)/glycoprotein-A repetitions predominant protein(GARP)/TGF-β/small mothers against decapentaplegic(SMAD)/epithelial-mesenchymal transition(EMT)分类
医药卫生引用本文复制引用
张升华,杨静怡,祁春晖,乔亮,高社干,齐义军..牙龈卟啉单胞菌通过GARP促进TGF-β/SMAD轴介导食管鳞状细胞癌细胞的上皮间质转化[J].中国肿瘤生物治疗杂志,2024,31(8):769-776,8.基金项目
国家自然科学基金(No.81872037) （No.81872037）
河南省医学科技攻关-省部共建重点项目(No.SBGJ202002100) （No.SBGJ202002100）
