The adhesin RadD enhances Fusobacterium nucleatum tumour colonization and colorectal carcinogenesis.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
21 Aug 2024
21 Aug 2024
Historique:
received:
22
11
2023
accepted:
15
07
2024
medline:
22
8
2024
pubmed:
22
8
2024
entrez:
21
8
2024
Statut:
aheadofprint
Résumé
Fusobacterium nucleatum can bind to host cells and potentiate intestinal tumorigenesis. Here we used a genome-wide screen to identify an adhesin, RadD, which facilitates the attachment of F. nucleatum to colorectal cancer (CRC) cells in vitro. RadD directly binds to CD147, a receptor overexpressed on CRC cell surfaces, which initiated a PI3K-AKT-NF-κB-MMP9 cascade, subsequently enhancing tumorigenesis in mice. Clinical specimen analysis showed that elevated radD gene levels in CRC tissues correlated positively with activated oncogenic signalling and poor patient outcomes. Finally, blockade of the interaction between RadD and CD147 in mice effectively impaired F. nucleatum attachment and attenuated F. nucleatum-induced oncogenic response. Together, our study provides insights into an oncogenic mechanism driven by F. nucleatum RadD and suggests that the RadD-CD147 interaction could be a potential therapeutic target for CRC.
Identifiants
pubmed: 39169124
doi: 10.1038/s41564-024-01784-w
pii: 10.1038/s41564-024-01784-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82250005
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82330086
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81830081
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82203227
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32100138
Organisme : Shanghai Science and Technology Development Foundation (Shanghai Science and Technology Development Fund)
ID : 20JC1410100
Organisme : China Postdoctoral Science Foundation
ID : 2022M712128
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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