Suppression of ??catenin signaling in colon carcinoma cells by a bacterial protein

Colorectal cancer is one of the leading causes cancer-related death worldwide. The adenomatous polyposis coli (APC) gene mutated in hereditary colorectal tumors and more than 80% sporadic tumors. APC mutations impair ?-catenin degradation, to its permanent stabilization increased transcription cancer-driving target genes. In colon cancer, impairment degradation leads cytoplasmic accumulation, nuclear translocation, subsequent activation tumor cell proliferation. Suppressing signaling cells therefore appears be a promising strategy for new anticancer strategies. Recently, we discovered novel Vibrio cholerae cytotoxin, motility-associated killing factor A (MakA), that affects both invertebrate vertebrate hosts. It promotes bacterial survival proliferation predators but has unknown biological role(s) mammalian Here, report MakA can cause lethality via induction apoptosis. Interestingly, exhibited potent cytotoxic activity, particular against several tested lines, while appearing less toxic toward nontransformed cells. bound surface became internalized into endolysosomal compartment induced leakage membranes, causing cytosolic release cathepsins proapoptotic proteins. addition, altered integrity cells, partly through caspase- proteasome-dependent mechanism. Importantly, inhibited ?-catenin-mediated Remarkably, intratumor injection significantly reduced development murine solid model. These data identify as candidate considered strategies therapeutic agents cancer.