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Esophageal cancer is one of the most aggressive cancers worldwide because of its distant metastasis at the time of diagnosis.Epithelial-mesenchymal transition(EMT)is the hallmark of tumor metastasis,characterized by changes in cell morphology and in the expression of lineage markers such as pan-cytokeratin and vimentin.CCAAT/enhancer binding protein beta(C/EBPβ)is a leucine-zipper transcription factor implicated in metabolism,development,cell growth and differentiation.However,its functions in esophageal squamous cell carcinoma(ESCC)remain largely unknown.Here,we investigated its role in EMT and the underlying mechanisms.Using an EGF-induced EMT model,we detected an increased level of C/EBPβ in esophageal squamous cell line EC109.Functionally down-regulation of C/EBPβ with specific RNA interference(siRNA)partially reversed EMT,in vitro study indicated C/EBPβ promoted invasion and metastasis of esophageal cancer cells.We further show that MiR-203,an important player involved in EMT,is a direct target of C/EBPβ.C/EBPβ can bind a distal regulatory element of miR-203 loci and decrease miR-203 expression as shown by ChIP assay and reporter gene assay.Mutation of C/EBPβ sumoylation site abolished the suppression effect of C/EBPβ on miR-203.Furthermore,E2F 1,another well documented player in EMT,and a recently discovered downstream gene of miR-203,is upregulated after C/EBPβ downregulated miR-203 expression.Our data suggested a C/EBPβ-miR-203-E2F1 axis regulate EMT in ESCC.