Cadherins in Tissue Organization

Cadherins are cell adhesion molecules that mediate selective adhesion between cells, establishing and maintaining tissue structures. During development, undifferentiated cells express specific cadherins as they differentiate into distinct tissue types, such as E-cadherins on epithelial cells and N-cadherins on neurons. This selective binding enables cells to sort and organize into proper tissues.

Cadherins exhibit homophilic binding, meaning cadherins on one cell bind to cadherins of the same or closely related type on another cell. Cells expressing higher cadherin levels segregate from those with lower levels. Both quantitative and qualitative specificity of cadherins help sort and organize cells into tissues, as demonstrated by early amphibian embryo experiments where dissociated cells reaggregated into tissue-like structures.

As the neural groove forms from the ectodermal layer, neural plate cells shift their cadherin expression from E-cadherin to N-cadherin. Cells at the neural plate border also start expressing other cadherins like cadherin 6B, bringing together the two ends and facilitating the pinching off of the neural tube. This dynamic cadherin switching enables the complex structural changes required for neural tube development.

Epithelial to mesenchymal transition (EMT) occurs when tumor cells stop expressing E-cadherin molecules, aided by transcription regulators like Twist. This loss of cell adhesion allows tumor cells to detach from neighboring cells and overcome tissue constraints. EMT is an essential step in the progression of tumor cells to malignant cells, enabling them to escape and invade other tissues.

Downregulation of cadherin expression leads to loss of cell adhesion, disrupting tissue integrity. Tumor cells that stop expressing cadherins can detach from neighboring cells and overcome tissue constraints. This breakdown of cadherin-mediated cell-cell adhesion is a critical mechanism that allows malignant cells to escape their tissue of origin and invade other tissues.

Experimentally blocking Twist in malignant breast cancer cells reduces their malignancy, demonstrating Twist's role in promoting EMT. Conversely, normal epithelial cells can be induced to undergo EMT by increasing Twist expression. These experiments show that Twist acts as a transcription regulator that inhibits E-cadherin expression, driving the transition to a mesenchymal phenotype.

Cadherins comprise a superfamily of over 180 variants, with specific tissues expressing a particular combination of cadherin types. This diversity allows cells to establish tissue-specific adhesion patterns. Different cadherin combinations enable selective cell-cell recognition and organization, ensuring that epithelial cells adhere to epithelial cells and neurons to neurons, maintaining proper tissue architecture.