A pro-carcinogenic oral microbe internalized by breast cancer cells promotes mammary tumorigenesis.

The intricate relationship between microbiota and breast cancer presents an additional risk factor that can have a profound impact on disease progression. Focusing on dysbiosis, our metagenomic analysis shows overabundance of an oral pathogenic microbe F. nucleatum and co-habitation of associated biofilm forming oral microbes in cancerous breast. Mammary gland colonization with F. nucleatum results in the development of metaplastic lesions accompanied with inflammation, DNA damage and hyper-proliferation in healthy mice. Exhibiting the impact of circulating F. nucleatum introduced via hematogenous route, breast tumor bearing mice show accelerated tumor growth and metastatic progression. Increased proliferation, migration, self-renewal and chemoresistance in breast cancer cells as well as non-tumorigenic breast epithelial cells bearing pathogenic BRCA1 mutation is observed upon F. nucleatum exposure which is internalized by the cells in a Gal-GalNAc dependent manner. Of interest, cells harboring BRCA1 mutations exhibit greater cell surface accumulation of Gal-GalNAc sugar residue. This work sheds light on the oncogenic impact of a pro-carcinogenic oral bacterium, F. nucleatum, on normal mammary epithelium and breast cancer, implicates the impairment of DNA damage and repair pathways as its functional mediators, and proposes the concept of increased vulnerability of BRCA1 mutant breast cancer cells owing to their preferential internalization of F. nucleatum.