E‐cadherin's role in development, tissue homeostasis and disease: Insights from mouse models

Abstract

Recent studies uncovered critical roles of the adhesion protein E-cadherin in health and disease. Global inactivation of Cdh1, the gene encoding E-cadherin in mice, results in early embryonic lethality due to an inability to form the trophectodermal epithelium. To unravel E-cadherin's functions beyond development, numerous mouse lines with tissue-specific disruption of Cdh1 have been generated. The consequences of E-cadherin loss showed great variability depending on the tissue in question, ranging from nearly undetectable changes to a complete loss of tissue structure and function. This review focuses on these studies and discusses how they provided important insights into E-cadherin's role in cell adhesion, proliferation and differentiation, and its consequences for biological processes as epithelial-to-mesenchymal transition, vascularization, and carcinogenesis. Lastly, we present some perspectives and possible approaches for future research.

Protective Effects of Ferulic Acid against Heat Stress-Induced Intestinal Epithelial Barrier Dysfunction In Vitro and In Vivo

“…Recent studies showed that heat stress decreased ZO-1 protein expression in Caco-2 cells [ 5 , 32 ]. Our results were consistent with this, showing that ZO-1 protein expression was significantly reduced in IEC-6 cells exposed to heat stress for 3 to 12 h. E-Cadherin is the major component of AJs, essential for intestinal development, homeostasis, and defense against pathogenic bacteria [ 26 , 27 ]. E-Cadherin facilitates assembly of specialized cellular junctions such as TJs and desmosomes, which together are required to connect epithelial cells into a functional monolayer [ 34 – 36 ].…”

“…TJ proteins include the transmembrane proteins occludin and claudins and the peripheral membrane proteins ZO-1 and ZO-2. E-cadherin is the major component of AJs, essential for intestinal development, homeostasis and the defense against pathogenic bacteria [ 26 , 27 ]. Because TJ and AJ proteins are involved in maintenance of epithelial barrier function, we investigated the role of TJ- and AJ-associated proteins, occludin, ZO-1 and E-cadherin, in the effects of heat stress in our model.…”

Elevated levels of Wnt signaling disrupt thymus morphogenesis and function

“…E-cadherin (encoded by the Cdh1 gene) is a classical cadherin involved in the formation of adherens junctions; its extracellular domain is composed of cadherin repeats that support homotypic interactions, its intracellular domain interacts with catenins in order to mediate connections with the cytoskeleton 26 . Previous studies demonstrated that E-cadherin is expressed by TECs 27 , and that blocking homotypic E-cadherin interactions prevents thymic lobe formation in re-aggregate thymus organ culture (RTOC) assays 28 , suggesting a functional role in thymus organogenesis.…”

Small molecule/ML327 mediated transcriptional de-repression of E-cadherin and inhibition of epithelial-to-mesenchymal transition

“…Epithelial-cadherin (E-cadherin, encoded by the CDH1 gene) is a key component of the adherens junction complex and plays a pivotal role in epithelial tissue architecture and cell differentiation. Since most solid tumors are carcinomas that are derived from epithelial cells/tissues that predominantly express E-cadherin, the capacity of these cells to undergo neoplastic transformation and to metastasize is often associated with the loss of expression of this protein [ 3 , 4 ].…”