免疫学杂志2024,Vol.40Issue(3) :225-233.DOI:10.13431/j.cnki.immunol.j.20240029

具核梭杆菌通过增强STAT6 O-GlcNAc糖基化修饰诱导巨噬细胞M2型极化最终促进结直肠癌转移

F.nucleatum promotes colorectal cancer metastases via macrophage STAT6 O-GlcNAcylation

张涛 唐彬 曾冬竹
免疫学杂志2024,Vol.40Issue(3) :225-233.DOI:10.13431/j.cnki.immunol.j.20240029

具核梭杆菌通过增强STAT6 O-GlcNAc糖基化修饰诱导巨噬细胞M2型极化最终促进结直肠癌转移

F.nucleatum promotes colorectal cancer metastases via macrophage STAT6 O-GlcNAcylation

张涛 1唐彬 2曾冬竹1
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作者信息

  • 1. 401120,重庆医科大学附属第三医院普外科
  • 2. 402260,重庆大学附属江津医院医学检验科
  • 折叠

摘要

目的 探讨具核梭杆菌(F.nucleatum)在巨噬细胞极化和结直肠癌转移中的作用及潜在的分子机制.方法 通过将F.nucleatum与RAW264.7细胞(MOI=100∶1)共培养,2-NBDG检测葡萄糖摄取,qPCR检测M1、M2型巨噬细胞的标志物,Western blot检测糖基化修饰水平以及巨噬细胞极化标志物,小麦胚芽凝集素(sWGA)下拉实验和免疫共沉淀(Co-IP)实验检测STAT6 O-GlcNAc糖基化修饰;其次,将F.nucleatum与RAW264.7细胞(MOI=100∶1)共培养,取其上清液制作条件培养基并处理RKO细胞后用划痕实验、Transwell实验检测细胞迁移和侵袭能力.结果 F.nucleatum促进巨噬细胞M2极化,且增强结直肠癌RKO细胞的迁移能力;F.nucleatum促进巨噬细胞对葡萄糖的摄取和巨噬细胞M2型相关标志物的表达,且促进STAT6 O-GlcNAc糖基化修饰.结论 F.nucleatum通过增强巨噬细胞葡萄糖摄取从而促进细胞内STAT6的O-GlcNAc糖基化修饰,进而诱导巨噬细胞向M2型极化最终促进结直肠癌的转移.

Abstract

This study was designed to explore the role of F.nucleatum in macrophage polarization and colorectal cancer metastasis.F.nucleatum and RAW264.7 cells were cocultured at the MOI of 100∶1,and then glucose uptake was measured by 2-NBDG,expression levels of M1 and M2 macrophage markers were determined by qPCR,glycosylation modification level and polarization marker expression of macrophages were tested by Western blotting,and STAT6 glycosylation modification was verified by Co-IP experiment.Meanwhile,F.nucleatum was co-cultured with RAW264.7(MOI=100∶1),and the supernatant was removed to treat RKO cells.The migration ability of colorectal cancer was detected by transwell experiment and scratch experiment.Data showed that F.nucleatum promoted M2 macrophage polarization and enhance the metastasis of colorectal cancer cells RKO;F.nucleatum also promoted the glucose intake of macrophages and enhanced the expression of M2-related markers.Taken together,F.nucleatum promotes the level of glycosylation in macrophages,which induces its polarization to M2 by modifying O-GlcNAc of STAT6,to regulate colorectal cancer metastasis.

关键词

结直肠癌/具核梭杆菌/巨噬细胞/糖基化修饰

Key words

Colorectal cancer/Fusobacterium nucleatum/Macrophage/O-GlcNAcylation

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基金项目

重庆市技术创新与应用发展面上项目(2023TIAD-GPX0126)

重庆市教委科学技术研究重点项目(KJZD-K202400102)

重庆大学附属江津医院院级科研培育项目(2023LJXM001)

重庆大学附属江津医院科研启动经费项目(2023qdjfxm002)

出版年

2024
免疫学杂志
第三军医大学,中国免疫学会

免疫学杂志

CSTPCD
影响因子:0.704
ISSN:1000-8861
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