Neutrophil extracellular traps mediate TLR9/Merlin axis to resist ferroptosis and promote triple negative breast cancer progression.
Ferroptosis
Neutrophil extracellular traps
TLR9/Merlin signaling
Triple negative breast cancer
Journal
Apoptosis : an international journal on programmed cell death
ISSN: 1573-675X
Titre abrégé: Apoptosis
Pays: Netherlands
ID NLM: 9712129
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
accepted:
14
06
2023
medline:
15
8
2023
pubmed:
27
6
2023
entrez:
27
6
2023
Statut:
ppublish
Résumé
Neutrophil and neutrophil extracellular traps (NETs) were reported to be associated with tumor development, but the exact role and concrete mechanisms are still poorly understood, especially in triple negative breast cancer (TNBC). In this study, our results exhibited that NETs formation in TNBC tissues was higher than that in non-TNBC tissues, and NETs formation was distinctly correlated with tumor size, ki67 level and lymph node metastasis in TNBC patients. Subsequent in vivo experiments demonstrated that NETs inhibition could suppress TNBC tumor growth and lung metastasis. Further in vitro experiments uncovered that oncogenic function of NETs on TNBC cells were possibly dependent on TLR9 expression. We also found that neutrophils from peripheral blood of TNBC patients with postoperative fever were prone to form NETs and could enhance the proliferation and invasion of TNBC cells. Mechanistically, we revealed that NETs could interact with TLR9 to decrease Merlin phosphorylation which contributed to TNBC cell ferroptosis resistance. Our work provides a novel insight into the mechanism of NETs promoting TNBC progression and blocking the key modulator of NETs might be a promising therapeutic strategy in TNBC.
Identifiants
pubmed: 37368176
doi: 10.1007/s10495-023-01866-w
pii: 10.1007/s10495-023-01866-w
doi:
Substances chimiques
Toll-Like Receptor 9
0
Neurofibromin 2
0
TLR9 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1484-1495Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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