Parida Sheetal, Wu Shaoguang, Siddharth Sumit, Wang Guannan, Muniraj Nethaji, Nagalingam Arumugam, Hum Christina, Mistriotis Panagiotis, Hao Haiping, Talbot C Conover, Konstantopoulos Konstantinos, Gabrielson Kathleen L, Sears Cynthia L, Sharma Dipali
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Cancer Discov. 2021 May;11(5):1138-1157. doi: 10.1158/2159-8290.CD-20-0537. Epub 2021 Jan 6.
The 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 with normal breast, we identified the presence of in cancerous breast. Mammary gland as well as gut colonization with enterotoxigenic (ETBF), which secretes 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 nontoxigenic . This work sheds light on the oncogenic impact of a procarcinogenic colon bacterium ETBF on breast cancer progression, implicates the β-catenin 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. SIGNIFICANCE: is an inhabitant of breast tissue, and gut or mammary duct colonization with ETBF triggers epithelial hyperplasia and augments breast cancer growth and metastasis. Short-term exposure to BFT elicits a "BFT memory" with long-term implications, functionally mediated by the β-catenin and Notch1 pathways..
不同的乳腺微生物群的存在最近已得到证实，但其对乳腺癌的生物学影响仍不清楚。我们聚焦于患病乳腺与正常乳腺微生物群落组成的变化，确定了癌性乳腺中存在[具体微生物未给出]。用分泌细胞毒素（BFT）的产肠毒素[具体细菌未给出]（ETBF）对乳腺以及肠道进行定殖，会迅速诱导乳腺上皮增生。暴露于BFT的乳腺癌细胞会表现出初始暴露后的“BFT记忆”。有趣的是，与无毒的[具体细菌未给出]相比，用ETBF对肠道或乳腺导管进行定殖会强烈诱导植入乳腺导管的肿瘤细胞生长和转移进展。这项工作揭示了致癌性结肠细菌ETBF对乳腺癌进展的致癌作用，表明β-连环蛋白和Notch1轴是其功能介质，并提出了“BFT记忆”的概念，该概念在初次暴露于ETBF后可能具有深远的生物学意义。意义：[具体细菌未给出]是乳腺组织的寄居菌，用ETBF对肠道或乳腺导管进行定殖会引发上皮增生并促进乳腺癌生长和转移。短期暴露于BFT会引发具有长期影响的“BFT记忆”，其功能由β-连环蛋白和Notch1途径介导。
