A new regulatory loop in cancer‐cell invasion

Abstract

The epithelial‐to‐mesenchymal transition (EMT) converts epithelial cells into mesenchymal cells that are able to invade and migrate. In the context of cancer pathogenesis, the EMT contributes to metastatic progression (Thiery, 2002; Acloque et al , 2008). One of the characteristics of EMT is the functional loss of E‐cadherin, which is crucial for the progression to invasive carcinoma (Perl et al , 1998). Transcriptional repression has emerged as a fundamental mechanism for E‐cadherin loss during EMT and several repressors have been characterized. These include zinc‐finger E‐box‐binding homeo box 1 (ZEB1), ZEB2/SIP1, Snail1, Snail2 and Twist, which strongly repress E‐cadherin transcription through their direct binding to the E‐box motifs within the E‐cadherin promoter (Barrallo‐Gimeno & Nieto, 2005; Peinado et al , 2007). During the past decade, it has emerged that microRNAs (miRNAs) are a fundamental mechanism of gene‐expression regulation, and several recent reports have shown that these small molecules are involved in the control of E‐cadherin expression in cancer cells and tumours (Hurteau et al , 2007; Christoffersen et al , 2007; Gregory et al , 2008; Park et al , 2008). Furthermore, in this issue of EMBO reports , Burk and colleagues have provided a beautiful example of gene regulation in which miRNAs and transcription factors are linked to one another in a gene‐regulatory network to control E‐cadherin expression and the invasive phenotype in cancer cells (Burk et al , 2008). MiRNAs regulate gene expression through binding to mRNA target sequences typically in their 3′ untranslated regulatory regions …