CDH2

CDH2 Full Name

cadherin 2, type 1, N-cadherin (neuronal)

CDH2 Introduction

The CDH2 gene encodes N-cadherin (neural cadherin), a classical type I transmembrane glycoprotein that mediates calcium-dependent, cell-cell adhesion. Like other classical cadherins, N-cadherin functions primarily through homophilic interactions, meaning the extracellular domain of an N-cadherin molecule on one cell specifically binds to an N-cadherin molecule on an adjacent cell.

Figure 1. Structure of E-cadherin and N-cadherin. (Source: Loh CY, et al. 2019)

Biologically, N-cadherin is absolutely essential during embryogenesis, particularly for the development of the central nervous system, where it regulates the migration of neurons and the formation of functional synapses. Beyond the nervous system, it is critically expressed in cardiac muscle cells, where it serves as a major structural component of the intercalated discs that physically couple beating cardiomyocytes together. In normal adult tissues, N-cadherin is primarily found in mesenchymal cells, fibroblasts, and endothelial cells, helping to maintain the structural integrity of these tissues.

In clinical pathology and oncology, N-cadherin is most notorious for its central role in the Epithelial-to-Mesenchymal Transition (EMT), a critical biological process co-opted by cancer cells. During tumor progression, malignant epithelial cells frequently undergo a "cadherin switch," wherein they downregulate the expression of the static E-cadherin (epithelial) and aberrantly upregulate N-cadherin (mesenchymal). This molecular switch profoundly alters the cell's adhesive affinity. Instead of binding tightly to neighboring epithelial cells, the tumor cells gain an affinity for the N-cadherin-rich stroma and endothelial cells, drastically enhancing their ability to invade surrounding tissues and enter the bloodstream. Consequently, aberrant N-cadherin expression is widely recognized as a biomarker for aggressive, metastatic phenotypes in various solid tumors, including prostate, breast, and pancreatic carcinomas. Furthermore, inherited mutations in the CDH2 gene have recently been linked to neurodevelopmental disorders and arrhythmogenic right ventricular cardiomyopathy (ARVC), emphasizing its structural importance in the heart and brain.

Alternate Names for CDH2

CDH2; cadherin 2, type 1, N-cadherin (neuronal); CDHN; NCAD; CD325; CDw325; cadherin-2; N-cadherin 1; neural cadherin; neural-cadherin; cadherin 2, N-cadherin (neuronal); calcium-dependent adhesion protein, neuronal;

• 1. Mrozik KM, et al. N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer. 2018 Oct 1;18(1):939.
  2. Loh CY, et al. The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. Cells. 2019 Sep 20;8(10):1118.