A pro-carcinogenic bacterial toxin binds claudin-4 to cleave E-cadherin.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42020735.
- Also identified by DOI 10.1038/s41586-026-10375-0 and PMC identifier 13253352.
- Licence recorded as CC BY-NC-ND.
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Abstract
The human colon is colonized by trillions of bacteria that play substantial roles in human health and disease<sup>1</sup>. Epidemiological and experimental studies suggest that certain colonic bacteria can stimulate the development and progression of colorectal cancer<sup>2</sup>. One such bacterium, enterotoxigenic Bacteroides fragilis, drives colon tumour formation through the action of a single toxin, the B. fragilis toxin (BFT)<sup>3,4</sup>. BFT is a metalloprotease that binds to a colonic epithelial cell receptor and causes cleavage of the E-cadherin ectodomain, leading to epithelial barrier disruption, inflammation and increased cellular proliferation<sup>4-6</sup>. However, the identity of the BFT receptor is unknown and the molecular mechanism of BFT-initiated E-cadherin cleavage is not well understood. Here we identify claudin-4 as a BFT receptor through a genome-wide CRISPR screen and demonstrate that claudin-4 binding promotes BFT-mediated cleavage of cell surface E-cadherin. Our work both sheds light on BFT's mechanism of action and opens avenues for the development of anti-BFT therapies, which may prove useful for colorectal cancer prevention and treatment of acute enterotoxigenic B. fragilis infection.
Medical subject headings
- Cadherins
- Claudin-4
- Bacterial Toxins
- Proteolysis
- Metalloendopeptidases