A pro-carcinogenic colon microbe promotes breast tumorigenesis and metastatic progression and concomitantly activates Notch and βcatenin axes

Abstract

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.