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The adenomatous polyposis coli (<jats:italic>APC<\/jats:italic>) gene is mutated in hereditary colorectal tumors and in more than 80% of sporadic colorectal tumors. APC mutations impair \u03b2\u2010catenin degradation, leading to its permanent stabilization and increased transcription of cancer\u2010driving target genes. In colon cancer, impairment of \u03b2\u2010catenin degradation leads to its cytoplasmic accumulation, nuclear translocation, and subsequent activation of tumor cell proliferation. Suppressing \u03b2\u2010catenin signaling in cancer cells therefore appears to be a promising strategy for new anticancer strategies. Recently, we discovered a novel <jats:italic>Vibrio cholerae<\/jats:italic> cytotoxin, motility\u2010associated killing factor A (MakA), that affects both invertebrate and vertebrate hosts. It promotes bacterial survival and proliferation in invertebrate predators but has unknown biological role(s) in mammalian hosts. Here, we report that MakA can cause lethality of tumor cells via induction of apoptosis. Interestingly, MakA exhibited potent cytotoxic activity, in particular against several tested cancer cell lines, while appearing less toxic toward nontransformed cells. MakA bound to the tumor cell surface became internalized into the endolysosomal compartment and induced leakage of endolysosomal membranes, causing cytosolic release of cathepsins and activation of proapoptotic proteins. In addition, MakA altered \u03b2\u2010catenin integrity in colon cancer cells, partly through a caspase\u2010 and proteasome\u2010dependent mechanism. Importantly, MakA inhibited \u03b2\u2010catenin\u2010mediated tumor cell proliferation. Remarkably, intratumor injection of MakA significantly reduced tumor development in a colon cancer murine solid tumor model. These data identify MakA as a novel candidate to be considered in new strategies for development of therapeutic agents against colon cancer.<\/jats:p>","DOI":"10.1002\/ijc.33562","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T10:07:44Z","timestamp":1615802864000},"page":"442-459","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Suppression of \u03b2\u2010catenin signaling in colon carcinoma cells by a bacterial protein"],"prefix":"10.1002","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1439-6216","authenticated-orcid":false,"given":"Aftab","family":"Nadeem","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and The Laboratory for Molecular Infection Medicine, Sweden (MIMS), Ume\u00e5 Centre for Microbial Research (UCMR) Ume\u00e5 University  Ume\u00e5 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