Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc

被引：708

作者：

Abed, Jawad ^{[1
]}

Emgard, Johanna E. M. ^{[1
]}

Zamir, Gideon ^{[2
]}

Faroja, Mouhammad ^{[2
]}

Almogy, Gideon ^{[2
]}

Grenov, Amalie ^{[1
]}

Sol, Asaf ^{[1
]}

Naor, Ronit ^{[1
]}

Pikarsky, Eli ^{[3
,4
]}

Atlan, Karine A. ^{[4
]}

Mellul, Anna ^{[4
]}

Chaushu, Stella ^{[5
]}

Manson, Abigail L. ^{[6
]}

Earl, Ashlee M. ^{[6
]}

Ou, Nora ^{[7
,8
]}

Brennan, Caitlin A. ^{[7
,8
]}

Garrett, Wendy S. ^{[6
,7
,8
,9
]}

Bachrach, Gilad ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Inst Dent Sci, IL-91120 Jerusalem, Israel

[2] Hadassah Hebrew Univ, Med Ctr, Dept Gen Surg, IL-91120 Jerusalem, Israel

[3] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Immunol & Canc Res, Inst Med Res Israel Canada, IL-91120 Jerusalem, Israel

[4] Hadassah Hebrew Univ, Med Ctr, Dept Pathol, IL-91120 Jerusalem, Israel

[5] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dept Orthodont, IL-91120 Jerusalem, Israel

[6] Broad Inst MIT & Harvard Univ, Cambridge, MA 02141 USA

[7] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA

[8] Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA

[9] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

来源：

CELL HOST & MICROBE | 2016年 / 20卷 / 02期

基金：

以色列科学基金会;

关键词：

PORPHYROMONAS-GINGIVALIS; MOLECULAR-FEATURES; CELL-ADHESION; E-CADHERIN; CANCER; DISEASE; IDENTIFICATION; TUMORIGENESIS; COAGGREGATION; ASSOCIATION;

D O I：

10.1016/j.chom.2016.07.006

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

Fusobacterium nucleatum is associated with colorectal cancer and promotes colonic tumor formation in preclinical models. However, fusobacteria are core members of the human oral microbiome and less prevalent in the healthy gut, raising questions about how fusobacteria localize to CRC. We identify a host polysaccharide and fusobacterial lectin that explicates fusobacteria abundance in CRC. Gal-GalNAc, which is overexpressed in CRC, is recognized by fusobacterial Fap2, which functions as a Gal-GalNAc lectin. F. nucleatum binding to clinical adenocarcinomas correlates with Gal-GalNAc expression and is reduced upon O-glycanase treatment. Clinical fusobacteria strains naturally lacking Fap2 or inactivated Fap2 mutants show reduced binding to Gal-GalNAc-expressing CRC cells and established CRCs in mice. Additionally, intravenously injected F. nucleatum localizes to mouse tumor tissues in a Fap2-dependent manner, suggesting that fusobacteria use a hematogenous route to reach colon adenocarcinomas. Thus, targeting F. nucleatum Fap2 or host epithelial Gal-GalNAc may reduce fusobacteria potentiation of CRC.

引用

页码：215 / 225

页数：11

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