title: Suppression of DACH1 promotes migration and invasion of colorectal cancer via activating TGF-β-mediated epithelial-mesenchymal transition.
abstract: 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 γ-catenin). Furthermore, EMT characteristics in DACH1-downregulated CRC cells were abrogated by TGF-β inhibitor SB431542. DACH1 overexpression reduced TGF-β-induced EMT and inhibited SW480 cell invasion which can be reversed in the presence of TGF-β. Thus, our results suggest that DACH1 loss of function results in increased cell growth, motility and invasiveness through TGF-β-mediated EMT, and DACH1 loss of function has important therapeutic implications for targeted therapies of CRC.
authors.affiliation: Department of Molecular Biology and Biochemistry of Weifang Medical College, Weifang, Shandong Province 261000, China. Electronic address: wangpingwfmc@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor; D002455:Cell Division; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology*; D017931:DNA Primers; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005136:Eye Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; C486747:DACH1 protein, human; D017931:DNA Primers; D005136:Eye Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta
keywords: Colorectal cancer; DACH1; EMT; Invasion; TGF-β