Back to Search
Start Over
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.
- 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.)
- Subjects :
- Animals
Female
Humans
Mice
Bacteroides fragilis chemistry
Cell Line, Tumor
Metalloendopeptidases pharmacology
Bacterial Toxins pharmacology
Breast Neoplasms microbiology
Breast Neoplasms pathology
Drug Resistance, Neoplasm drug effects
Neoplastic Stem Cells drug effects
Nod1 Signaling Adaptor Protein antagonists & inhibitors
Nod1 Signaling Adaptor Protein genetics
Nod1 Signaling Adaptor Protein metabolism
Subjects
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