Twist-related protein 1-mediated regulation of mesenchymal change contributes to the migration and invasion of cervical cancer cells.

Abstract

Twist-related protein 1 (Twist1), is a class II basic helix-loop-helix transcription factor, which has been demonstrated to be a major regulator of epithelial-mesenchymal transition (EMT), and therefore is involved in promoting carcinoma metastasis. Previous studies have demonstrated that Twist1 expression is upregulated in cervical cancer cases with poor clinical outcomes. However, the mechanisms that mediate the role of Twist1 in cervical cancer metastasis are poorly understood. To the best of our knowledge, the present study provides the first evidence that the downregulation of Twist1 by short hairpin RNA lentivirus (LV-shRNA) resulted in the inhibition of invasion and migration of cervical cancer cells. Furthermore, the present study presents evidence that reducing Twist1 expression prevents cervical cancer cells from undergoing EMT. The expression of the epithelial cell marker, E-cadherin, was elevated; and the expression levels of mesenchymal cell markers [fibronectin, vimentin, matrix metalloproteinase-9 (MMP-9) and MMP-2] were reduced in the LV-sh-Twist1 group in cervical cells. Collectively, these findings indicate that Twist1-mediated modulation of EMT is important in the invasion and migration of cervical cells, and also indicates the potential therapeutic importance of strategies involving the inactivation of Twist1-mediated mesenchymal changes in cervical cancer.