Cadherin-2 (Neural cadherin) (CDH2)

Cadherin-2 (Neural cadherin), commonly referred to as N-cadherin, is a calcium-dependent transmembrane glycoprotein belonging to the classical cadherin family that facilitates homophilic cell-cell adhesion [2][18]. It is predominantly expressed in the nervous system, cardiac muscle, and mesenchymal tissues, where it is essential for embryonic development, tissue morphogenesis, and maintaining structural integrity, particularly in the heart [8][9][11]. Beyond its structural role, N-cadherin acts as a signaling platform that modulates pathways such as Wnt/beta-catenin and interacts with the fibroblast growth factor receptor (FGFR) to promote cell survival and differentiation [3][10][16]. In pathology, N-cadherin is a key driver of the epithelial-to-mesenchymal transition (EMT), a process where tumor cells lose epithelial markers and gain mesenchymal properties to enhance their motility, invasion, and metastatic potential [5][20]. It is upregulated in aggressive cancers, including prostate cancer, melanoma, and glioblastoma, and it also mediates protective interactions between leukemia cells and the bone marrow microenvironment [1][3][10]. Therapeutic strategies targeting N-cadherin involve the use of antagonists like ADH-1 (Exherin) and LCRF-0006, which competitively inhibit the His-Ala-Val (HAV) adhesion motif to disrupt tumor cell clusters and inhibit angiogenesis [3][10][13]. While targeting N-cadherin offers potential for treating metastatic disease and fibrosis, considerations regarding its physiological roles in the vasculature, heart, and blood-brain barrier are critical for drug safety and development [8][12][21].

Other names

N-cadherinNeural cadherinCD325CDHNNCADCalcium-dependent adhesion protein, neuronalCadherin-2, type 1CDw325

Competitive inhibition of homophilic cell-cell adhesion through binding to the HAV (His-Ala-Val) motif and modulation of downstream signaling pathways, including FGFR and Wnt/beta-catenin.