DACH1 has been found down-regulated in a variety of human cancers, but its clinical significance and functional roles in colorectal cancer (CRC) remain unknown. In this study, we identified DACH1 as a tumor suppressor in CRC. Suppression of DACH1 strikingly increased cell growth, migration and invasion potential of CRC cell line SW480. Expression analysis of a set of epithelial-mesenchymal transition (EMT) markers by RT-qPCR and western blot showed an increase in the expression of mesenchymal markers (vimentin and N-cadherin) and a reduction in the expression of epithelial marker (E-cadherin and gamma-catenin). Furthermore, EMT characteristics in DACH1-downregulated CRC cells were abrogated by TGF-beta inhibitor SB431542. DACH1 overexpression reduced TGF-beta-induced EMT and inhibited SW480 cell invasion which can be reversed in the presence of TGF-beta. Thus, our results suggest that DACH1 loss of function results in increased cell growth, motility and invasiveness through TGF-beta-mediated EMT, and DACH1 loss of function has important therapeutic implications for targeted therapies of CRC. (C) 2015 Published by Elsevier Inc.