E-cadherin

E-cadherin

E-cadherin (epithelial cadherin) is a protein that in humans is encoded by the CDH1 gene. It is a type of cadherin, which are a class of type-1 transmembrane proteins. E-cadherin is critically involved in cell-cell adhesion, ensuring that cells within tissues are bound together. It is a key component in maintaining the structure and function of epithelial tissues.

Structure

E-cadherin is a classical cadherin, which means it is a calcium-dependent adhesion molecule. The protein is composed of several domains:

• **Extracellular domain**: This domain contains five cadherin repeats, which are responsible for homophilic binding to E-cadherin molecules on adjacent cells.
• **Transmembrane domain**: This hydrophobic region anchors the protein in the cell membrane.
• **Cytoplasmic domain**: This domain interacts with catenins, linking E-cadherin to the actin cytoskeleton and playing a role in signal transduction.

Function

E-cadherin is essential for the formation and maintenance of adherens junctions, which are crucial for the integrity of epithelial layers. It mediates cell-cell adhesion by forming homophilic interactions with E-cadherin molecules on neighboring cells. This adhesion is calcium-dependent, as calcium ions stabilize the extracellular domain of E-cadherin.

E-cadherin also plays a role in:

• **Cell signaling**: It is involved in signaling pathways that regulate cell proliferation, differentiation, and survival.
• **Development**: E-cadherin is crucial during embryonic development, particularly in processes such as gastrulation and the formation of the neural tube.
• **Tumor suppression**: Loss of E-cadherin function is associated with increased invasiveness and metastasis of cancer cells.

Clinical Significance

Mutations in the CDH1 gene, which encodes E-cadherin, are linked to several diseases, including:

• **Hereditary diffuse gastric cancer (HDGC)**: Germline mutations in CDH1 are associated with an increased risk of developing diffuse gastric cancer and lobular breast cancer.
• **Breast cancer**: Loss of E-cadherin expression is often observed in invasive lobular carcinoma of the breast.

E-cadherin is also a marker for epithelial-mesenchymal transition (EMT), a process by which epithelial cells lose their cell-cell adhesion properties and gain migratory and invasive characteristics. EMT is a critical step in cancer metastasis.

Research and Therapeutic Implications

Research into E-cadherin has significant implications for cancer therapy. Restoring E-cadherin function or preventing its loss may help inhibit tumor progression and metastasis. Therapeutic strategies include:

• **Gene therapy**: Introducing functional CDH1 genes into cancer cells.
• **Small molecules**: Developing drugs that enhance E-cadherin expression or function.

See Also

• Cadherin
• Adherens junction
• Epithelial-mesenchymal transition