Fusobacterium nucleatum Fap2 lectin (Fap2)

Fusobacterium nucleatum Fap2 lectin, also known as Fibroblast activation protein 2, is a large (~390 kDa) outer membrane autotransporter protein that serves as a critical virulence factor for the bacterium (3.1.4, 3.4.1). It functions as a bifunctional adhesin, specifically recognizing and binding to the carbohydrate moiety Gal-GalNAc (D-galactose-β(1-3)-N-acetyl-D-galactosamine), which is overexpressed on the surface of colorectal cancer (CRC) cells and other adenocarcinomas (2.3.1, 2.3.3). This interaction facilitates the 'precision homing' and colonization of F. nucleatum in tumor tissues, where the bacterium promotes tumor progression, metastasis, and chemoresistance (2.3.4, 3.4.3). Additionally, Fap2 interacts with the inhibitory receptor TIGIT on natural killer (NK) cells and T lymphocytes, leading to the suppression of host anti-tumor immunity (2.1.1, 3.1.5). Due to its central role in bacterial recruitment to tumors and immune evasion, Fap2 is considered a promising therapeutic target for the treatment of F. nucleatum-associated cancers, with strategies including the development of inhibitory antibodies, small molecules, and vaccines (3.2.2, 3.3.1).

Other names

Fibroblast activation protein 2Fap2 proteinGal-GalNAc-binding lectinGalactose-inhibitable adhesinFusobacterium autotransporter protein 2

Fap2 mediates bacterial recruitment to tumors by binding to Gal-GalNAc on cancer cells and inhibits host anti-tumor immunity by activating the TIGIT receptor on NK and T cells (2.1.1, 2.3.1, 3.4.4).