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Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1.

Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1.

Authors :
Ma W
Zhang L
Chen W
Chang Z
Tu J
Qin Y
Yao Y
Dong M
Ding J
Li S
Li F
Deng Q
Yang Y
Feng T
Zhang F
Shao X
He X
Zhang L
Hu G
Liu Q
Jiang YZ
Zhu S
Xiao Z
Su D
Liu T
Liu S
Source :
Protein & cell [Protein Cell] 2024 May 28; Vol. 15 (6), pp. 419-440.
Publication Year :
2024

Abstract

Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant progression. However, targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail. Here, we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis (ETBF) was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy. ETBF, albeit at low biomass, secreted the toxic protein BFT-1 to promote breast cancer cell stemness and chemoresistance. Mechanistic studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 protein. NOD1 was highly expressed on ALDH+ breast cancer stem cells (BCSCs) and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation, thereby activating the NOTCH1-HEY1 signaling pathway to increase BCSCs. NOD1 inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.<br /> (© The Author(s) 2024. Published by Oxford University Press on behalf of Higher Education Press.)

Details

Language :
English
ISSN :
1674-8018
Volume :
15
Issue :
6
Database :
MEDLINE
Journal :
Protein & cell
Publication Type :
Academic Journal
Accession number :
38437016
Full Text :
https://doi.org/10.1093/procel/pwae005