Transcription factors controlling E-cadherin downregulation in ovarian cancer

Abstract

© The Author(s) 2018. Transcription factors (TFs), such as Snail, Slug and Twist, control the down-regulation of cell-cell adhesion molecule Ecadherin in ovarian cancer. Low E-cadherin aids tumour cells in undergoing epithelial-mesenchymal transition (EMT) to motile morphology, disseminating to other organs. High TF levels have also correlated with chemoresistance and poor prognosis. This review aims to discern mechanisms of E-cadherin reduction by TFs and identifies hypoxia-inducible factor 1α (HIF1α) as an upstream regulator in hypoxic conditions. Association with chemoresistance is investigated, and whether its reversal is possible. Snail was found to bind more strongly to the E-cadherin promoter than Slug; it was suggested that Snail maintained EMT whilst Slug induced it. The use of differential zinc fingers by Snail and Slug to bind to the E-cadherin promoter supported this. HIF1α was shown to lie upstream of all three TFs and protein degradation or post-transcriptional regulation using miR-548c may regulate of Twist downstream. Further study into this is needed. High Snail expression correlated with cisplatin resistance, with knockdown of Snail reversing it. The same may be true for Twist and Slug, though some studies conflicted this. These findings show promising potential of TFs and HIF1α as therapeutic targets for EMT prevention and even chemoresistance reversal.