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

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外文摘要：Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant progression.However,tar-geting microbiota to improve the effects of breast cancer therapy has not been investigated in detail.Here,we eval-uated 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 pro-mote 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.

外文关键词：

microbiotaETBFBFT-1NOD1breast cancer stem cellchemoresistance

作者：

Wei Ma、Lu Zhang、Weilong Chen、Zhaoxia Chang、Juchuanli Tu、Yuanyuan Qin、Yuwen Yao、Mengxue Dong、Jiajun Ding、Siqin Li、Fengkai Li、Qiaodan Deng、Yifei Yang、Tingting Feng、Fanrong Zhang、Xiying Shao、Xueyan He、Lixing Zhang、Guohong Hu、Quentin Liu、Yi-Zhou Jiang、Shu Zhu、Zhi Xiao、Dan Su、Tong Liu、Suling Liu

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作者单位：

Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences,State Key Laboratory of Genetic Engineering,Cancer Institutes,Department of Oncology,Key Laboratory of Breast Cancer in Shanghai,The Shanghai Key Laboratory of Medical Epigenetics,Shanghai Key Laboratory of Radiation Oncology,The International Co-laboratory of Medical Epigenetics and Metabolism,Ministry of Science and Technology,Shanghai Medical College,Fudan University,Shanghai 200032,China

Intelligent Pathology Institute and Depar

Department of Thyroid,Breast and Vascular

Institute of Immunology,CAS Key Laboratory of Innate Immunity and Chronic Disease,School of Basic Medical Sciences,Division of Life Science and Medicine,University of Science and Technology of China,Hefei 230027,China

Department of Pathology,The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital),Institute of Basic Medicine and Cancer(IBMC),Chinese Academy of Sciences,Hangzhou 310022,China

Department of Breast Surgery,The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital),Institute of Basic Medicine and Cancer(IBMC),Chinese Academy of Sciences,Hangzhou 310022,China

Department of Breast Medical Oncology,The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital),Institute of Basic Medicine and Cancer(IBMC),Chinese Academy of Sciences,Hangzhou 310022,China

Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China

Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Guangzhou 510060,China

Department of Breast Surgery,Xiangya Hospital,Changsha 410008,China

Department of Breast Surgery,Tumor Hospital of Harbin Medical University,Harbin 150081,China

Translational Medicine Research and Cooperation Center of Northern China,Heilongjiang Academy of Medical Sciences,Harbin 150081,China

Jiangsu Key Lab of Cancer Biomarkers,Prev

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基金：

National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of China"Ten Thousand Plan"—National High-Level Talents Special Support PlanProgram of Shanghai Academic/Technology Research LeaderProgram for Outstanding Medical Academic Leader in Shanghaiinnovative research team of highlevel local university in ShanghaiFudan University Research FoundationResearch Foundation of the Fudan University Shanghai Cancer CenterShanghai Anticancer Association EYAS PROJECTNatural Science Foundation of Hunan Province

项目编号：

2023YFC25064002020YFA01123008223010381930075820732678220339982072903WR-YK520210120XD14007002019LJ04IDH1340042YJRC1603SACA-CY23B072020JJ4916

出版年：

2024

DOI：

10.1093/procel/pwae005

蛋白质与细胞

CSTPCD

影响因子：0.645

ISSN：

年,卷(期)：2024.15(6)