- N-cadherin, a type of cadherin that mediates calcium-dependent cell-cell adhesion, plays a crucial role in epithelial-to-mesenchymal transition (EMT) by facilitating the transition from a tightly adherent epithelial state to a more migratory mesenchymal phenotype. Unlike its epithelial counterpart, E-cadherin, which is downregulated during EMT, N-cadherin is upregulated, and its expression correlates with the acquisition of mesenchymal characteristics. This switch from E-cadherin to N-cadherin is considered a critical aspect of EMT, as it allows cells to lose their epithelial adhesiveness and gain the ability to migrate and invade.
- N-cadherin is primarily involved in cell-cell adhesion in mesenchymal tissues, and its upregulation during EMT allows cells to form more loose, migratory junctions, facilitating cell detachment and motility. This transition is particularly important in cancer metastasis, where cells must detach from the primary tumor, invade the surrounding stroma, and migrate to distant organs. The replacement of E-cadherin by N-cadherin also contributes to changes in the cytoskeleton, promoting actin remodeling and enhancing the contractility of mesenchymal cells, which is essential for their invasive capabilities.
- The expression of N-cadherin during EMT is regulated by EMT-inducing transcription factors, such as Snail, Slug, Twist, and ZEB1, which repress epithelial markers like E-cadherin and induce the expression of mesenchymal markers, including N-cadherin. These transcription factors are activated by various extracellular signals, including growth factors like TGF-β, Wnt, and FGF, which are involved in processes like wound healing, fibrosis, and cancer progression. Additionally, signaling through notch pathways and vascular endothelial growth factor (VEGF) has been implicated in N-cadherin induction during EMT.
- In the context of cancer, the increased expression of N-cadherin is often associated with enhanced cell motility, invasion, and metastatic potential. For example, in breast cancer, glioblastoma, and non-small cell lung cancer, upregulation of N-cadherin has been linked to poor prognosis, as it promotes the invasive behavior of tumor cells. Similarly, in fibrotic diseases, where tissue remodeling and scarring occur, elevated N-cadherin expression contributes to the fibroblast-like phenotype of epithelial cells and the development of fibrosis. In chronic inflammatory conditions, the aberrant expression of N-cadherin has been shown to promote cell migration and tissue remodeling, which may facilitate disease progression.
- Overall, N-cadherin serves as both a marker and a functional mediator of EMT, contributing to the morphological and behavioral changes that allow epithelial cells to transition to a mesenchymal phenotype. Its role in cell-cell adhesion, migration, and invasion makes it a key player in developmental processes, wound healing, cancer metastasis, and other pathological conditions.
