Bacteroides Fragilis enterotoxin engagement of the colonic epithelium is associated with early YAP1 activation and colon tumorigenesis

Here, wild-type BFT2, but not catalytically inactive BFT2, induced E-cadherin loss and nuclear accumulation of active YAP1 in colonic epithelial cells. Deletion of BFT receptors, CLAUDINs 3 and 4 mitigated BFT-associated E-cadherin loss and YAP1 nuclear translocation, supporting a model in which BFT epithelial targeting is linked to early YAP1 activation.

In ETBF-colonized Min mice, epithelial YAP1 activation was rapid and transient, whereas STAT3 and NF-kB activation persisted after colonization. Nevertheless, conditional deletion of epithelial Yap1 was sufficient to abrogate colon tumor formation without altering ETBF colonization or abolishing IL-17 colitis. Transcriptomic analyses further associated epithelial Yap1 deficiency with reduced regenerative epithelial programs and increased secretory-cell differentiation signatures.