N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signalling

Abstract

Cell migration is a process which is essential during embryonic development, throughout adult life and in some pathological conditions. Cadherins, and more specifically the neural cell adhesion molecule N-cadherin, play an important role in migration. In embryogenesis, N-cadherin is the key molecule during gastrulation and neural crest development. N-cadherin mediated contacts activate several pathways like Rho GTPases and function in tyrosine kinase signalling (for example via the fibroblast growth factor receptor). In cancer, cadherins control the balance between suppression and promotion of invasion. E-cadherin functions as an invasion suppressor and is downregulated in most carcinomas, while N-cadherin, as an invasion promoter, is frequently upregulated. Expression of N-cadherin in epithelial cells induces changes in morphology to a fibroblastic phenotype, rendering the cells more motile and invasive. However in some cancers, like osteosarcoma, N-cadherin may behave as a tumour suppressor. N-cadherin can have multiple functions: promoting adhesion or induction of migration dependent on the cellular context. KEY WORDS: N-cadherin, cancer, embryogenesis, invasion, signallingInt. J. Dev. Biol. 48: 463-476 (2004) Migration and invasionCell migration is a process that is essential during embryonic development and throughout further life. In the adult, cell migration is crucial for homeostatic processes, such as effective immune responses and repair of injured tissues. To migrate, the individual cell body must modify its shape to interact with the surrounding tissue structures. The extracellular matrix (ECM) forms a substrate, as well as a barrier for the advancing cell body. Cell migration through tissues results from a continuous cycle of interdependent steps. In general, there are five steps involved in cell migration in the ECM. First comes the protrusion of the leading edge, where growing actin filaments connect to adapter proteins and push the cell membrane in an outward direction. In a second step cell-matrix interactions and focal contacts are formed. After that, surface proteases such as matrix metalloproteinases (MMP) are recruited and focal proteolysis takes place. Then the cell contracts by actomyosin activation, and finally the tail of the cell is detached from its substrate (Friedl and Wolf, 2003).Border cells of the Drosophila melanogaster ovary are nowadays used as a model for migration. There are three recently discovered signalling pathways that control distinct aspects of migration: a global steroid-hormone signal defines the timing of migration, a highly localised cytokine signal that activates the Janus kinase-signal transducer and activator of transcription is both necessary and sufficient to induce migration, and finally, a growth factor that is analogous to platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) contributes to guiding the cells to their destination (Montell, 2003).In embryonic morphogenesis two types of collective cell movement can ...

Optimedin induces expression of N-cadherin and stimulates aggregation of NGF-stimulated PC12 cells

“…Upregulation of N-cadherin occurred at both mRNA and protein levels under physiological levels of Ca 2+ . A number of transcription and growth factors are implicated in the regulation of Ncadherin gene expression [44]. At present, we don't understand how optimedin expression may up-regulate expression of the N-cadherin gene or increase stability of N-cadherin mRNA.…”

Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression

“…Over 30 classical cadherins (also known as type I cadherins) have been described; however the most prevalent are epithelial (E)-cadherin and neuronal (N)-cadherin. E-cadherin is found in adherens junctions of most polarized epithelial cells while N-cadherin is found in neural tissues, cardiac and skeletal muscle, some mesenchymal tissues and mesothelium [40,41]. Cadherins are comprised of five conserved extracellular tandem repeats, a single pass transmembrane domain and a conserved intracellular catenin binding domain that provides a mechanism for linking cell-cell adhesion to other intracellular structural and signaling complexes [42].…”

S1P induced changes in epithelial ovarian cancer proteolysis, invasion, and attachment are mediated by Gi and Rac

“…While E-cadherin suppresses invasion and is downregulated in most cancers, N-cadherin encourages invasion and is usually upregulated in malignant cells [25]. N-cadherin is present in the membranes of DOV 13 cells, while OVCA 429 membranes contain E-cadherin.…”