CDH24

CDH24 Full Name

cadherin 24, type 2

CDH24 Introduction

CDH24 encodes cadherin-24, a calcium-dependent cell adhesion molecule of the type II classical cadherin family that helps cells recognize and adhere to one another during tissue formation and homeostasis. Cadherins are the principal adhesion receptors of adherens junctions, and they do far more than glue cells together: by engaging the same cadherin on a neighboring cell, they generate adhesive contacts that organize the actin cytoskeleton and relay signals that influence cell shape, polarity, proliferation, and survival. As a type II cadherin, cadherin-24 lacks the histidine-alanine-valine (HAV) adhesion motif characteristic of type I cadherins and instead uses a distinct interface, and its expression is dynamically regulated during development in tissues such as the nervous system and the gut. In the adult, CDH24 is found in a range of epithelial and other tissues, and its downregulation is a common feature of epithelial cancers, where loss of homotypic adhesion is thought to contribute to the detachment, invasion, and metastasis of tumor cells. Conversely, altered or ectopic cadherin expression can also promote the aggressive behavior of certain tumor cells by enabling them to adhere to and invade surrounding stroma. Because cadherin switching is one of the hallmarks of the epithelial-mesenchymal transition that underlies metastasis, understanding cadherin-24 function is important for cancer biology and for the design of therapies that restore adhesive barriers to tumor spread.

Figure 1. The structure of CDH24.

Classical Cadherin Architecture and Adhesive Mechanism
Cadherin-24 is a single-pass type I transmembrane glycoprotein whose large extracellular region is organized into five tandem cadherin (EC) repeats.
Each EC repeat adopts a beta-barrel fold stabilized by calcium ions bound at the interdomain boundaries; calcium binding rigidifies the extracellular region and is absolutely required for adhesion.
Adhesion is mediated by the exchange of strands between the N-terminal EC1 domains of cadherins on opposing cells, a 'strand-swap' mechanism that generates strong, specific homotypic binding.
The CDH24 gene is located on human chromosome 14 and is classified within the type II cadherin subfamily, whose members generally mediate more dynamic adhesion than their type I counterparts.
The short cytoplasmic tail of cadherin-24 binds catenins, linking the adhesion complex to the actin cytoskeleton and to signaling pathways that sense cell contact.
p120-catenin binding to the juxtamembrane region stabilizes the cadherin and regulates its trafficking, while beta-catenin couples the complex to actin through alpha-catenin.
The adhesive strength of cadherin-24, like that of other classical cadherins, is regulated by the density of receptors at the cell surface and by the organization of the underlying actin cytoskeleton.

Tissue Development, Cancer Progression, and Adhesion Signaling
During development, cadherin-24 is expressed in a spatiotemporally controlled manner in the nervous system and in other tissues, where it is thought to contribute to the sorting and cohesion of cells that must organize into distinct structures.
The dynamic regulation of cadherin expression allows cells to change their adhesive partners during morphogenetic movements, a process that is recapitulated aberrantly during tumor invasion.
In many epithelial cancers, including colorectal and gastric carcinomas, CDH24 expression is reduced as tumor cells lose their epithelial character, and this loss correlates with features of the epithelial-mesenchymal transition.
Experimental manipulation of cadherin-24 in cancer cell lines alters their adhesive capacity, migration, and invasive behavior, although the direction of the effect depends on the cellular context and on which cadherins are co-expressed.
The balance between different cadherin family members, rather than the level of any single cadherin, determines the adhesive phenotype of a tumor cell, and cadherin switching is used clinically as an indicator of tumor aggressiveness.
Efforts to understand cadherin-24 signaling are therefore directed both at the basic mechanisms of cell-cell adhesion and at the ways in which tumors subvert these mechanisms to invade and metastasize.

Alternate Names for CDH24

CDH24; cadherin 24, type 2; CDH11L; cadherin-24;