We showed that loss of epithelial characteristics and simultaneous gain of mesenchymal features correlated with CYTOR expression. Knockdown of CYTOR attenuated colon cancer cell migration and invasion. Conversely, ectopic expression of CYTOR induced an EMT program and enhanced metastatic properties of colon cancer cells. Mechanistically, the binding of CYTOR to cytoplasmic B-catenin impeded casein kinase 1 (CK1)-induced B-catenin phosphorylation that enabled it to accumulate and translocate to the nucleus. Reciprocally, B-catenin/TCF complex enhanced the transcription activity of CYTOR in nucleus, thus forming a positive feed-forward circuit. Moreover, elevated CYTOR, alone or combined with overexpression of nuclear B-catenin, was predictive of poor prognosis. Our findings suggest that CYTOR promotes colon cancer EMT and metastasis by interacting with B-catenin, and the positive feed-forward circuit of CYTOR-B-catenin might be a useful therapeutic target in antimetastatic strategy.