Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis

被引:36
|
作者
Chen, Gang [1 ,2 ]
Gao, Chunna [2 ]
Jiang, Shan [1 ]
Cai, Qiaoling [3 ]
Li, Rongrong [4 ]
Sun, Qiang [5 ]
Xiao, Can [6 ]
Xu, Yubo [2 ,9 ]
Wu, Buling [1 ,10 ]
Zhou, Hongwei [7 ,8 ,11 ]
机构
[1] Southern Med Univ, Shenzhen Stomatol Hosp Pingshan, Shenzhen 518118, Peoples R China
[2] Tongji Univ, Shanghai East Hosp, Dept Stomatol, Sch Med, Shanghai 200120, Peoples R China
[3] Xiamen Univ, Dept Hematol, Affiliated Hosp 1, Xiamen, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Oral & Maxillofacial Head & Neck Oncol, Shanghai 200011, Peoples R China
[5] Zhengzhou Univ, Dept Transfus, Affiliated Hosp 1, Zhengzhou 450052, Peoples R China
[6] Soochow Univ, Dept Oncol, Affiliated Hosp 1, Suzhou 215006, Peoples R China
[7] Southern Med Univ, Zhujiang Hosp, Microbiome Med Ctr, Dept Lab Med, Guangzhou 510655, Guangdong, Peoples R China
[8] Southern Med Univ, Guangdong Prov Inst Nephrol, State Key Lab Organ Failure Res, Guangzhou 510515, Peoples R China
[9] Tongji Univ, Shanghai East Hosp, Dept Stomatol, Sch Med, Shanghai, Peoples R China
[10] Southern Med Univ, Shenzhen Stomatol Hosp Pingshan, Shenzhen, Peoples R China
[11] Southern Med Univ, Zhujiang Hosp, Microbiome Med Ctr, Div Lab Med,State Key Lab Organ Failure Res, Guangzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
Fusobacterium nucleatum; Autophagy; Outer membrane vesicles; Epithelial-mesenchymal transition; COLORECTAL-CANCER;
D O I
10.1016/j.jare.2023.04.002
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Introduction: Metastasis is an important cause of high mortality and lethality of oral cancer. Fusobacterium nucleatum (Fn) can promote tumour metastasis. Outer membrane vesicles (OMVs) are secreted by Fn. However, the effects of Fn-derived extracellular vesicles on oral cancer metastasis and the underlying mechanisms are unclear. Objectives: We aimed to determine whether and how Fn OMVs mediate oral cancer metastasis. Methods: OMVs were isolated from brain heart infusion (BHI) broth supernatant of Fn by ultracentrifugation. Tumour-bearing mice were treated with Fn OMVs to evaluate the effect of OMVs on cancer metastasis. Transwell assays were performed to determine how Fn OMVs affect cancer cell migration and invasion. The differentially expressed genes in Fn OMV-treated/untreated cancer cells were identified by RNA-seq. Transmission electron microscopy, laser confocal microscopy, and lentiviral transduction were used to detect changes in autophagic flux in cancer cells stimulated with Fn OMVs. Western blotting assay was performed to determine changes in EMT-related marker protein levels in cancer cells. Fn OMVs' effects on migration after blocking autophagic flux by autophagy inhibitors were determined by in vitro and in vivo experiments. Results: Fn OMVs were structurally similar to vesicles. In the in vivo experiment, Fn OMVs promoted lung metastasis in tumour-bearing mice, while chloroquine (CHQ, an autophagy inhibitor) treatment reduced the number of pulmonary metastases resulting from the intratumoral Fn OMV injection. Fn OMVs promoted the migration and invasion of cancer cells in vivo, leading to altered expression levels of EMTrelated proteins (E-cadherin downregulation; Vimentin/N-cadherin upregulation). RNA-seq showed that Fn OMVs activate intracellular autophagy pathways. Blocking autophagic flux with CHQ reduced in vitro and in vivo migration of cancer cells induced by Fn OMVs as well as reversed changes in EMT-related protein expression. Conclusion: Fn OMVs not only induced cancer metastasis but also activated autophagic flux. Blocking (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article
引用
收藏
页码:167 / 179
页数:13
相关论文
共 50 条
  • [1] FUSOBACTERIUM NUCLEATUM SECRETES OUTER MEMBRANE VESICLES AND PROMOTES INTESTINAL INFLAMMATION
    Engevik, Melinda A.
    Danhof, Heather
    Ruan, Wenly
    Goodwin, Annie G.
    Britton, Robert A.
    Versalovic, James
    GASTROENTEROLOGY, 2020, 158 (06) : S205 - S205
  • [2] Fusobacterium nucleatum Secretes Outer Membrane Vesicles and Promotes Intestinal Inflammation
    Engevik, Melinda A.
    Danhof, Heather A.
    Ruan, Wenly
    Engevik, Amy C.
    Chang-Graham, Alexandra L.
    Engevik, Kristen A.
    Shi, Zhongcheng
    Zhao, Yanling
    Brand, Colleen K.
    Krystofiak, Evan S.
    Venable, Susan
    Liu, Xinli
    Hirschi, Kendal D.
    Hyser, Joseph M.
    Spinler, Jennifer K.
    Britton, Robert A.
    Versalovic, James
    MBIO, 2021, 12 (02): : 1 - 17
  • [3] Outer membrane vesicles from Fusobacterium nucleatum aggravate rheumatoid arthritis
    Li, Ru
    RHEUMATOLOGY & AUTOIMMUNITY, 2023, 3 (04): : 255 - 256
  • [4] Quantitative Proteomic Analysis of Outer Membrane Vesicles from Fusobacterium nucleatum Cultivated in the Mimic Cancer Environment
    Zhang, Xuqiang
    Wang, Yuxin
    Fan, Ruochen
    Zhang, Liying
    Li, Zhuting
    Zhang, Yanmei
    Zheng, Wei
    Wang, Lulu
    Liu, Baoquan
    Quan, Chunshan
    MICROBIOLOGY SPECTRUM, 2023, 11 (04):
  • [5] Fusobacterium Nucleatum Metabolites and Outer Membrane Vesicles Drive Intestinal Inflammation In Vitro and In Vivo
    Engevik, Melinda A.
    Danhof, Heather A.
    Ruan, Wenly
    Engevik, Amy C.
    Chang-Graham, Alexandra L.
    Engevik, Kristen A.
    Shi, Zhongcheng
    Zhao, Yanling
    Hyser, Joseph M.
    Spinler, Jennifer K.
    Britton, Robert A.
    Versalovic, James
    AMERICAN JOURNAL OF PATHOLOGY, 2020, 190 (12): : S10 - S10
  • [6] Porphyromonas gingivalis outer membrane vesicles inhibit the invasion of Fusobacterium nucleatum into oral epithelial cells by downregulating FadA and FomA
    Zhang, Zhiying
    Liu, Sai
    Zhang, Shuwei
    Li, Yuchao
    Shi, Xiaoting
    Liu, Dongjuan
    Pan, Yaping
    JOURNAL OF PERIODONTOLOGY, 2022, 93 (04) : 515 - 525
  • [7] Fusobacterium nucleatum aggravates rheumatoid arthritis through FadA-containing outer membrane vesicles
    Hong, Mukeng
    Li, Zhuang
    Liu, Haihua
    Zheng, Songyuan
    Zhang, Fangling
    Zhu, Junqing
    Shi, Hao
    Ye, Haixing
    Chou, Zhantu
    Gao, Lei
    Diao, Jianxin
    Zhang, Yang
    Zhang, Dongxin
    Chen, Shixian
    Zhou, Hongwei
    Li, Juan
    CELL HOST & MICROBE, 2023, 31 (05) : 798 - +
  • [8] Proteomic characterization of outer membrane vesicles from gut mucosa-derived fusobacterium nucleatum
    Liu, Jinjing
    Hsieh, Ching-Lin
    Gelincik, Ozkan
    Devolder, Bryan
    Sei, Shizuko
    Zhang, Sheng
    Lipkin, Steven M.
    Chang, Yung-Fu
    JOURNAL OF PROTEOMICS, 2019, 195 : 125 - 137
  • [9] Outer Membrane Vesicles Derived From Fusobacterium nucleatum Trigger Periodontitis Through Host Overimmunity
    Zhang, Li
    Zhang, Demao
    Liu, Chengcheng
    Tang, Boyu
    Cui, Yujia
    Guo, Daimo
    Duan, Mengmeng
    Tu, Ying
    Zheng, Huiling
    Ning, Xinjie
    Liu, Yang
    Chen, Haoran
    Huang, Minglei
    Niu, Zhixing
    Zhao, Yanfang
    Liu, Xiaoheng
    Xie, Jing
    ADVANCED SCIENCE, 2024, 11 (47)
  • [10] Fusobacterium nucleatum apoptosis-inducing outer membrane protein
    Kaplan, CW
    Lux, R
    Huynh, T
    Jewett, A
    Shi, W
    Haake, SK
    JOURNAL OF DENTAL RESEARCH, 2005, 84 (08) : 700 - 704