Microbial metabolite ammonia disrupts TGF-β signaling to promote colon cancer.

ABSTRACT: Colorectal cancer (CRC) is rising alarmingly in younger populations, potentially arising from factors, such as obesity, proinflammatory gut microbiome, and the accumulation of toxic metabolites. However, how metabolites such as ammonia impact key signaling pathways to promote CRC remains unclear. Our study investigates a critical link between gut microbiome alterations, ammonia, and their toxic effects on the transforming growth factor beta (TGF-β) signaling pathway, driving CRC progression. We observed altered microbial populations in an obesity-induced mouse model of cancer, where ammonia promotes caspase-3-mediated cleavage of the SMAD3 adaptor βII-spectrin (SPTBN1). Cleaved SPTBN1 fragments form adducts with ammonia that induce proinflammatory cytokine expression and disrupt TGF-β sign

SUBMITTER: Bhowmick K 

PROVIDER: S-EPMC12155590 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature