Cadherin-1

Adherens-junction

Chromogenic immunohistochemistry for E-cadherin in invasive lobular carcinoma, annotated

Cadherin-1, also known as E-cadherin (epithelial cadherin), is a protein that in humans is encoded by the CDH1 gene. E-cadherin is a cellular adhesion molecule that plays a crucial role in cell adhesion, forming adherens junctions to bind cells within tissues together. It is a type of cadherin and is involved in the regulation of cellular morphology and cellular signaling, playing a key role in the maintenance of tissue architecture and the establishment of cell polarity.

Function

E-cadherin is a transmembrane protein that mediates calcium-dependent cell-cell adhesion in epithelial tissues. It is essential for the maintenance of the epithelial barrier function, cellular differentiation, and tissue homeostasis. The extracellular domain of E-cadherin interacts with E-cadherin molecules on adjacent cells, while its intracellular domain interacts with catenins, which connect to the actin cytoskeleton, providing mechanical strength to the adhesion complex. Disruption of E-cadherin-mediated adhesion can lead to increased cellular motility and invasion, processes often associated with cancer progression.

Clinical Significance

Alterations in the CDH1 gene, including mutations and reduced expression, have been implicated in a variety of cancers, notably gastric cancer, breast cancer, and colorectal cancer. Loss of E-cadherin function is considered a hallmark of epithelial-mesenchymal transition (EMT), a process by which epithelial cells acquire migratory and invasive properties. In the context of cancer, EMT contributes to tumor metastasis. Germline mutations in the CDH1 gene are associated with hereditary diffuse gastric cancer (HDGC) syndrome, a condition that significantly increases the risk of developing diffuse gastric cancer and lobular breast cancer.

Genetics

The CDH1 gene is located on the long (q) arm of chromosome 16 at position 22.1, denoted as 16q22.1. It consists of multiple exons that encode the E-cadherin protein. Genetic variations in CDH1, including single nucleotide polymorphisms (SNPs) and mutations, can affect the function and expression of E-cadherin, contributing to disease susceptibility and progression.

Therapeutic Implications

Given its role in cancer progression and metastasis, E-cadherin is a potential target for cancer therapy. Strategies to enhance E-cadherin expression or function could potentially inhibit tumor growth and metastasis. However, therapeutic targeting of E-cadherin and the pathways regulating its expression and function requires further research to understand its complex role in cancer and other diseases.

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