产毒素脆弱拟杆菌促进乳腺癌的发生和转移
- ①比较正常乳腺和乳腺癌中的菌群，发现乳腺癌中存在脆弱拟杆菌；
- ②乳腺和肠内定植的产肠毒素脆弱拟杆菌（ETBF）可快速分泌脆弱拟杆菌毒素（BFT），诱导乳腺增生；
- ③BFT诱导正常乳腺上皮细胞和乳腺癌细胞发生形态和功能变化，提高干细胞特征促进多灶性乳腺肿瘤发生；
- ④短期BFT暴露能诱导乳腺癌细胞长期的“BFT记忆”，由β-catenin和Notch1介导；
- ⑤相比于非毒性脆弱拟杆菌，ETBF在肠道或乳腺导管的定植能促进植入乳腺癌细胞的生长和转移。
主编推荐语
乳腺中存在不同的微生物群，但它们在乳腺癌中的生物学功能还有待研究。Cancer Discovery近期发表的文章，发现脆弱拟杆菌可定位于乳腺组织，肠道或乳腺导管定位的产肠毒素脆弱拟杆菌诱导乳腺上皮增生，增加乳腺癌生长和转移。此外，短期的脆弱拟杆菌暴露可诱发长期的“BFT记忆“，且 由β-catenin和Notch1信号介导。
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A pro-carcinogenic colon microbe promotes breast tumorigenesis and metastatic progression and concomitantly activates Notch and βcatenin axes
一种致癌的结肠微生物促进乳腺癌的发生和转移，同时激活Notch和β-catenin轴
10.1158/2159-8290.CD-20-0537
2021-01-06, Article
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Existence of distinct breast microbiota has been recently established but their biological impact in breast cancer remains elusive. Focusing on the shift in microbial community composition in diseased breast compared to normal breast, we identified the presence of Bacteroides fragilis in cancerous breast. Mammary gland as well as gut-colonization with enterotoxigenic Bacteroides fragilis (ETBF), that secretes B. fragilis toxin (BFT), rapidly induces epithelial hyperplasia in the mammary gland. Breast cancer cells exposed to BFT exhibit 'BFT-memory' from the initial exposure. Intriguingly, gut or breast-duct colonization with ETBF strongly induces growth and metastatic progression of tumor cells implanted in mammary ducts in contrast to non-toxigenic Bacteroides fragilis. This work sheds light on the oncogenic impact of a pro-carcinogenic colon bacterium ETBF, on breast cancer progression, implicates βcatenin and Notch1 axis as its functional mediators, and proposes the concept of 'BFT-memory' that can have far-reaching biological implications after initial exposure to ETBF.
First Authors:
Sheetal Parida
Correspondence Authors:
Dipali Sharma
All Authors:
Sheetal Parida,Shaoguang Wu,Sumit Siddharth,Guannan Wang,Nethaji Muniraj,Arumugam Nagalingam,Christina Hum,Panagiotis Mistriotis,Haiping Hao,C Conover Talbot,Konstantinos Konstantopoulos,Kathleen L Gabrielson,Cynthia L Sears,Dipali Sharma
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