1.17.6 Cadherin Definition

Cadherin Definition is a description of a class of cell-cell adhesion molecule that mediates physical attachment between adjacent cells through a binding mechanism dependent on the presence of calcium ions, in which a cadherin molecule on the surface of one cell binds directly to a corresponding cadherin molecule presented on the surface of a neighboring cell, forming a homophilic interaction in which the binding partner is typically the same type of cadherin molecule on both cells.

Conceptual Basis

Calcium-Dependent Binding

A cadherin is defined by its requirement for calcium ions in order to adopt the structural conformation necessary for stable binding to its partner cadherin molecule, such that the presence of calcium is essential to cadherin-mediated adhesion, and removal of calcium disrupts the structural integrity required for this binding to occur.

Homophilic Binding Specificity

A cadherin molecule characteristically binds most stably to a cadherin molecule of the same specific type presented on an adjoining cell, a pattern termed homophilic binding, in contrast to adhesion mechanisms in which the binding partners on the two interacting surfaces are structurally distinct from one another.

Structural Basis

Extracellular Binding Region

The portion of a cadherin extending outward from the cell surface is structured to engage in calcium-dependent binding with a corresponding cadherin molecule on an adjacent cell, forming the direct physical linkage responsible for cadherin-mediated cell-cell adhesion.

Intracellular Region Linked to the Cytoskeleton

The portion of a cadherin extending into the interior of the cell is coupled, through a set of intracellular adaptor proteins, to the internal actin cytoskeletal framework, mechanically linking the cell-cell adhesive contact to the cell's internal structural network and thereby reinforcing the stability of the adhesive junction.

Functional Roles

Establishing Stable Cell-Cell Contacts

Because cadherin binding is homophilic and calcium-dependent, matching populations of the same cadherin type on adjoining cells produce a specific and stable pattern of cell-cell attachment, contributing directly to the formation and maintenance of organized, coherent tissue structure.

Coupling Adhesion to Intracellular Signaling

Beyond their structural adhesive function, cadherins and their associated intracellular adaptor proteins participate in signaling processes influenced by the state of cell-cell contact, such that engagement of cadherin-mediated adhesion can influence downstream cellular behavior including proliferation.

Relationship to Cell-Cell Adhesion and Cancer Cell Biology

A Principal Mediator of Cell-Cell Adhesion

Cadherins constitute a principal class of adhesion molecule mediating cell-cell adhesion, providing the specific, calcium-dependent homophilic binding interactions through which cells attach to their neighbors and thereby contribute to the establishment of organized tissue structure.

Consequences of Reduced Cadherin Function in Cancer Cells

Because cadherin-mediated adhesion normally restrains cell movement and maintains stable tissue integration, reduced expression or function of cadherins is closely associated with the capacity of cancer cells to detach from neighboring cells and behave in a more independent, mobile manner, positioning altered cadherin function as a significant contributor to the invasive and disseminated behavior characteristic of cancer cell adhesion.