Bacterial toxin hijacks claudin-4 to cleave E-cadherin, fueling colorectal cancer risk
Researchers identify claudin-4 as the receptor for enterotoxigenic Bacteroides fragilis toxin (BFT) and show that BFT binding to claudin-4 enables direct cleavage of the E-cadherin ectodomain at the cell surface, disrupting the epithelial barrier and triggering pro-carcinogenic signaling. A genome-wide CRISPR screen highlighted claudin-4 as a key determinant of BFT toxicity, with validation in multiple cell lines and a mouse model. Importantly, a soluble claudin-4 analogue blocks BFT activity both in vitro and in vivo, suggesting a potential therapeutic approach to prevent ETBF-associated colorectal neoplasia and infection.