29.3:
Cadherins in Tissue Organization
Cadherins, a class of cell adhesion molecules, mediate selective adhesion between cells and thus, play a crucial role in establishing and maintaining tissue structures.
During development, undifferentiated cells express specific cadherins on their surface as they differentiate into distinct tissue types, such as E-cadherins on epithelial cells and N-cadherins on neurons.
Because cadherins generally bind other cadherins of the same type, cells can selectively adhere to each other.
Additionally, cells expressing higher cadherin levels segregate from those with lower levels.
Thus, both quantitative and qualitative specificity of cadherins help sort and organize the cells into tissues.
Conversely, the downregulation of cadherin expression leads to the loss of cell adhesion.
For instance, tumor cells that stop expressing cadherins can detach from neighboring cells and overcome the tissue constraints.
This transition, called epithelial to mesenchymal transition or EMT, is an essential step in the progression of tumor cells to malignant cells.
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.
Suggested Reading
- Paulson, Alicia F., et al. "Regulation of cadherin expression in nervous system development." Cell adhesion & migration 8.1 (2014): 19-28.
- Berx, Geert, and Frans Van Roy. "Involvement of members of the cadherin superfamily in cancer." Cold Spring Harbor perspectives in biology 1.6 (2009): a003129.