The Y-box binding protein-1 (YB-1) is a transcription/translation regulatory protein, and the expression thereof is associated with cancer aggressiveness. In the present study, we explored the regulatory effects of YB-1 during the transforming growth factor-beta 1 (TGF-beta 1)-induced epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma cells. Downregulation of YB-1 increased E-cadherin promoter activity, and upregulation of YB-1 decreased promoter activity, suggesting that the YB-1 level may be correlated with the EMT. TGF-beta 1 induced YB-1 expression, and TGF-beta 1 translocated cytosolic YB-1 into the nucleus. YB-1 overexpression promoted TGF-beta 1-induced downregulation of epithelial markers, upregulation of mesenchymal markers, and cell migration. Moreover, YB-1 overexpression enhanced the expression of E-cadherin transcriptional repressors via TGF-beta 1-induced Akt activation. Our findings afford new insights into the role played by YB-1 in the TGF-beta 1 signaling pathway. (C) 2015 Elsevier Inc. All rights reserved.