Abstract
Epithelial tissues rely on the adhesion between participating cells to retain their integrity. The transmembrane protein E-cadherin is the major protein that mediates homophilic adhesion between neighbouring cells and is, therefore, one of the critical components for epithelial integrity. E-cadherin downregulation has been described extensively as a prerequisite for epithelial-to-mesenchymal transition and is a hallmark in many types of cancer. Due to this clinical importance, research has been mostly focused on understanding the mechanisms leading to transcriptional repression of this adhesion molecule. However, in recent years it has become apparent that re-expression of E-cadherin is a major step in the progression of many cancers during metastasis. Here, we review the currently known molecular mechanisms of E-cadherin transcriptional activation and inhibition and highlight complex interactions between individual mechanisms. We then propose an additional mechanism, whereby the competition between adhesion complexes and heterochromatin protein-1 for binding to STAT92E fine-tunes the levels of E-cadherin expression in Drosophila but also regulates other genes promoting epithelial robustness. We base our hypothesis on both existing literature and our experimental evidence and suggest that such feedback between the cell surface and the nucleus presents a powerful paradigm for epithelial resilience.
Highlights
Cells in epithelia adhere to both a common substrate and neighbouring cells (Hagios et al, 1998). The molecules mediating this adhesion are the driving force behind the tissue architecture (Gumbiner, 1996; Buckley et al, 1998; Hagios et al, 1998; Schock and Perrimon, 2002), whereas adhesion defects often occur during tumour formation and metastasis (Zetter, 1993; Janiszewska et al, 2020)
We focus on Epithelial cadherin (E-cadherin, E-cad), as in epithelial cells, it plays a major role in tissue formation and maintenance (Takeichi, 1977; Halbleib and Nelson, 2006; Nelson, 2008; Kaszak et al, 2020)
Other cadherins such as P-cadherin do contribute to cell–cell adhesion in epithelia but their actions are restricted to specific areas and developmental stages (Paredes et al, 2012)
Summary
Cells in epithelia adhere to both a common substrate and neighbouring cells (Hagios et al, 1998). The best-studied regulation of E-cad transcription in mammalian cells is silencing by transcription factors (TFs) including SNAIL, SLUG ( known as SNAI1 and SNAI2 in mammals), ZEB1/2, and Twist1/2 (Figure 1A), all of which directly bind conserved E-boxes (CANNTG sequences) in the E-cad promoter (Giroldi et al, 1997; Comijn et al, 2001; Bolós et al, 2003; Wong et al, 2014; Vergara et al, 2016; Russell and Pranjol, 2018).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
