Abstract
Fusobacterium nucleatum has emerged as a key microbial contributor to colorectal cancer (CRC) progression through immune modulation and tumor colonization. Its outer membrane adhesin Fap2 functions as a bifunctional lectin that recognizes tumor-associated glycans and engages immune inhibitory receptors. Recent structural insights reveal a unique β-helical architecture enabling simultaneous binding to Gal-GalNAc moieties on tumor cells and TIGIT on immune cells. This dual interaction underpins bacterial tropism to CRC and facilitates immune evasion. Here, we synthesize structural, functional, and translational insights into Fap2 biology, highlighting therapeutic strategies targeting the Fap2–TIGIT axis and identifying gaps in small-molecule inhibition, particularly from natural products.
