Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression

Lishay Parhi, Tamar Alon-Maimon, Asaf Sol, Deborah Nejman, Amjad Shhadeh, Tanya Fainsod-Levi, Olga Yajuk, Batya Isaacson, Jawad Abed, Naseem Maalouf, Aviram Nissan, Judith Sandbank, Einav Yehuda-Shnaidman, Falk Ponath, Jörg Vogel, Ofer Mandelboim, Zvi Granot, Ravid Straussman, Gilad Bachrach*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Fusobacterium nucleatum is an oral anaerobe recently found to be prevalent in human colorectal cancer (CRC) where it is associated with poor treatment outcome. In mice, hematogenous F. nucleatum can colonize CRC tissue using its lectin Fap2, which attaches to tumor-displayed Gal-GalNAc. Here, we show that Gal-GalNAc levels increase as human breast cancer progresses, and that occurrence of F. nucleatum gDNA in breast cancer samples correlates with high Gal-GalNAc levels. We demonstrate Fap2-dependent binding of the bacterium to breast cancer samples, which is inhibited by GalNAc. Intravascularly inoculated Fap2-expressing F. nucleatum ATCC 23726 specifically colonize mice mammary tumors, whereas Fap2-deficient bacteria are impaired in tumor colonization. Inoculation with F. nucleatum suppresses accumulation of tumor infiltrating T cells and promotes tumor growth and metastatic progression, the latter two of which can be counteracted by antibiotic treatment. Thus, targeting F. nucleatum or Fap2 might be beneficial during treatment of breast cancer.

Original languageEnglish
Article number3259
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - 1 Dec 2020
Externally publishedYes

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