Correlation between DEC1/DEC2 and epithelial-mesenchymal transition in human prostate cancer PC-3 cells

Abstract

Differentiated embryonic chondrocyte (DEC) genes have been reported to be involved in the regulation of mammalian circadian rhythms, differentiation, apoptosis, the response to hypoxia and epithelial-mesenchymal transition (EMT). Activation of transforming growth factor (TGF)-β signaling is known to promote EMT for the development of metastatic castration-resistant prostate cancer (PCa). However, the role of DEC genes in the TGF-β-induced EMT of PCa remains unclear. In the present study it was demonstrated that TGF-β increased the transcriptional/translational levels of DEC1 but decreased those of DEC2 in PC-3 cells. Moreover, TGF-β evoked the phosphorylation of Smad2, followed by the activation of mesenchymal markers, such as N-cadherin and vimentin, in addition to the suppression of epithelial markers, such as E-cadherin. The knockdown of DEC1 restrained TGF-β-induced cell morphology changes as well as cell motility, which was compatible with the upregulation of E-cadherin and downregulation of pSmad2, N-cadherin, and vimentin. However, DEC2 knockdown endorsed PC-3 cells with a more metastatic phenotype. EMT-related markers in DEC2 siRNA-transfected cells exhibited a reverse expression pattern when compared with that in DEC1 siRNA-transfected cells. Taken together, these results provide evidence that DEC1 and DEC2 have opposite effects on TGF-β-induced EMT in human prostate cancer PC-3 cells.