Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis
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 un...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123223000942 |
| _version_ | 1797338343234600960 |
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| author | Gang Chen Chunna Gao Shan Jiang Qiaoling Cai Rongrong Li Qiang Sun Can Xiao Yubo Xu Buling Wu Hongwei Zhou |
| author_facet | Gang Chen Chunna Gao Shan Jiang Qiaoling Cai Rongrong Li Qiang Sun Can Xiao Yubo Xu Buling Wu Hongwei Zhou |
| author_sort | Gang Chen |
| collection | DOAJ |
| description | 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 EMT-related 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 autophagic flux weakened Fn OMV-stimulated cancer metastasis. |
| first_indexed | 2024-03-08T09:29:45Z |
| format | Article |
| id | doaj.art-3a1c4f6a95594846ba2ef4afe5fc3b5d |
| institution | Directory Open Access Journal |
| issn | 2090-1232 |
| language | English |
| last_indexed | 2024-03-08T09:29:45Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj.art-3a1c4f6a95594846ba2ef4afe5fc3b5d2024-01-31T05:42:56ZengElsevierJournal of Advanced Research2090-12322024-02-0156167179Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasisGang Chen0Chunna Gao1Shan Jiang2Qiaoling Cai3Rongrong Li4Qiang Sun5Can Xiao6Yubo Xu7Buling Wu8Hongwei Zhou9Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, Shenzhen 518118, China; Department of Stomatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, ChinaDepartment of Stomatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, ChinaShenzhen Stomatology Hospital (Pingshan), Southern Medical University, Shenzhen 518118, ChinaDepartment of Stomatology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, ChinaDepartment of Oral and Maxillofacial Head and Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDepartment of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, ChinaDepartment of Stomatology, the First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Stomatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Corresponding authors at: Department of Stomatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (Yubo Xu), Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, Shenzhen (Buling Wu), Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, Guangdong (Hongwei Zhou).Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, Shenzhen 518118, China; Corresponding authors at: Department of Stomatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (Yubo Xu), Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, Shenzhen (Buling Wu), Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, Guangdong (Hongwei Zhou).Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510655, China; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, Guangdong 510515, China; Corresponding authors at: Department of Stomatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China (Yubo Xu), Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, Shenzhen (Buling Wu), Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, Guangdong (Hongwei Zhou).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 EMT-related 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 autophagic flux weakened Fn OMV-stimulated cancer metastasis.http://www.sciencedirect.com/science/article/pii/S2090123223000942Fusobacterium nucleatumAutophagyOuter membrane vesiclesEpithelial-mesenchymal transition |
| spellingShingle | Gang Chen Chunna Gao Shan Jiang Qiaoling Cai Rongrong Li Qiang Sun Can Xiao Yubo Xu Buling Wu Hongwei Zhou Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis Journal of Advanced Research Fusobacterium nucleatum Autophagy Outer membrane vesicles Epithelial-mesenchymal transition |
| title | Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis |
| title_full | Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis |
| title_fullStr | Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis |
| title_full_unstemmed | Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis |
| title_short | Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis |
| title_sort | fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis |
| topic | Fusobacterium nucleatum Autophagy Outer membrane vesicles Epithelial-mesenchymal transition |
| url | http://www.sciencedirect.com/science/article/pii/S2090123223000942 |
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