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         description: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. High levels of Fusobacterium nucleatum have been associated with poor overall survival in patients with colorectal and esophageal cancer. Here, the authors show that F. nucleatum is abundant in breast cancer samples and that the colonization by F. nucleatum accelerates tumor growth and metastasis in preclinical breast cancer models.
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      headline:Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression
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            address:
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            address:
               name:Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Center for Infection Research (HZI), Würzburg, Germany
               type:PostalAddress
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            address:
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      affiliation:
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            address:
               name:Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel
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            address:
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            address:
               name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
               type:PostalAddress
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      affiliation:
            name:The Hebrew University-Hadassah School of Dental Medicine
            address:
               name:The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
               type:PostalAddress
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      email:[email protected]
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      name:The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
      name:The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
      name:The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
      name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
      name:The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
      name:Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel
      name:Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel
      name:Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel
      name:The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
      name:The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
      name:Department of General and Oncological Surgery-Surgery C, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
      name:The Pathology Institute, Maccabi Healthcare Services, Rehovot, Israel
      name:The Pathology Institute, Maccabi Healthcare Services, Rehovot, Israel
      name:Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Center for Infection Research (HZI), Würzburg, Germany
      name:Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Center for Infection Research (HZI), Würzburg, Germany
      name:Institute for Molecular Infection Biology, Medical Faculty, University of Würzburg, Würzburg, Germany
      name:Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel
      name:Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel
      name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
      name:The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel

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