The transcription factor Slug represses<i>E-cadherin</i>expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors

TLDR

Transcriptional repression of E‑cadherin, a key step in development and tumor progression, is mediated by factors such as Snail, E12/E47, ZEB‑1, and SIP‑1 that bind proximal E‑box elements of its promoter. Slug represses E‑cadherin by binding to proximal E‑box motifs, particularly the E‑pal element, on the mouse promoter. Slug functions as an E‑cadherin repressor, fully silencing its transcription in MDCK cells and inducing epithelial‑to‑mesenchymal transition, though it binds the E‑pal element with lower affinity than Snail or E47, suggesting that its in‑vivo activity depends on relative concentrations and cellular context.

Abstract

Transcriptional repression mechanisms have emerged as one of the crucial processes for the downregulation of E-cadherin expression during development and tumour progression. Recently, several E-cadherin transcriptional repressors have been characterized (Snail, E12/E47, ZEB-1 and SIP-1) and shown to act through an interaction with proximal E-boxes of the E-cadherin promoter. We have analyzed the participation of another member of the Snail family, Slug, and observed that it also behaves as a repressor of E-cadherin expression. Stable expression of Slug in MDCK cells leads to the full repression of E-cadherin at transcriptional level and triggers a complete epithelial to mesenchymal transition. Slug-induced repression of E-cadherin is mediated by its binding to proximal E-boxes, particularly to the E-pal element of the mouse promoter. Detailed analysis of the binding affinity of different repressors to the E-pal element indicates that Slug binds with lower affinity than Snail and E47 proteins. These results, together with the known expression patterns of these factors in embryonic development and carcinoma cell lines, support the idea that the in vivo action of the different factors in E-cadherinrepression can be modulated by their relative concentrations as well as by specific cellular or tumour contexts.