N-cadherin as a key regulator of collective cell migration in a 3D environment.
Cell migration is a critical step of normal developmental processes and disease progression. Often, migrating cells interact and maintain contact with neighboring cells. However, the precise roles of cell-cell adhesion in cell migration have thus far been poorly defined. Often in aggressive cancers, N-cadherin is prominently upregulated, yet, these highly motile cells have limited cell-cell adhesion when plated on a stiff 2D substrate. But, the same cells in a 3D matrix migrate as a multicellular cluster. This new observation suggests that N-cadherin-mediated cell-cell adhesion supports cell interactions between migrating cells in a more physiologically relevant 3D matrix, but not on a 2D substrate. While N-cadherin is an integral part of neural synapses, the ectopic expression of N-cadherin in transformed epithelial cells plays an equally important part in initiating pro-migratory signaling, and providing strong yet flexible cell cohesion essential for persistent cell migration in a 3D matrix. The 3D cell migration analysis for studying cell-to-cell interactions exposes the roles of N-cadherin in multicellular migration, and reveals novel insights into cell migration-dependent normal and pathological processes.
Department of Biomedical Engineering, University of California, Davis, CA USA.
Wenting
W
Shih
Soichiro
S
Yamada
D008841:Actin Cytoskeleton; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002450:Cell Communication; D002465:Cell Movement; D048430:Cell Shape; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D017434:Protein Structure, Tertiary; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C107953:RAC1 protein, human; D017468:Receptors, Fibroblast Growth Factor; D020830:rac1 GTP-Binding Protein