29.3 : Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.

Cell Sorting During Development

Cell sorting plays an essential role during embryogenesis and development, as demonstrated by early experiments with amphibian embryos. Cells from young embryos were dissociated and allowed to mix. When this mix was allowed to aggregate, similar cells grouped together, forming structures. These structures resembled embryonic layers such as the mesoderm, epidermis, and neural tube. Cadherin expression changes as the cells differentiate during development, enabling the formation of complex structures such as the neural tube of vertebrates. As the neural groove forms from the ectodermal layer, the neural plate cells shift their cadherin expression from E-cadherin to N-cadherin. The cells at the neural plate border also start expressing other cadherins like cadherin 6B, thus bringing together the two ends and facilitating the pinching off of the neural tube.

Cadherins and Malignancy

Cadherin-mediated cell-cell adhesion is an important mechanism that maintains tissue homeostasis in multicellular organisms. In cancerous tissues, however, this cell adhesion breaks down. Many epithelial tumor cells stop expressing E-cadherin molecules, partially or entirely, aided by various transcription regulators. For example, a transcription regulator called Twist inhibits the expression of E-cadherin, thus preventing the tumor cells from adhering to the neighboring cells. This transformation is called the epithelial to mesenchymal transition (EMT). It is a characteristic feature of progression to malignancy that allows tumor cells to escape and invade other tissues. Experimentally blocking Twist in malignant breast cancer cells reduces their malignancy. In contrast, normal epithelial cells can be induced to undergo EMT by increasing Twist expression.