Transforming growth factor beta controls the directional migration of hepatocyte cohorts by modulating their adhesion to fibronectin.
Transforming growth factor beta (TGF-beta) has a strong impact on liver development and physiopathology, exercised through its pleiotropic effects on growth, differentiation, survival, and migration. When exposed to TGF-beta, the mhAT3F cells, immortalized, highly differentiated hepatocytes, maintained their epithelial morphology and underwent dramatic alterations of adhesion, leading to partial or complete detachment from a culture plate, followed by readhesion and spreading. These alterations of adhesive behavior were caused by sequential changes in expression of the alpha5beta1 integrin and of its ligand, the fibronectin. The altered specificity of anchorage to the extracellular matrix gave rise to changes in cells' collective motility: cohorts adhering to fibronectin maintained a persistent, directional motility, with ezrin-rich pathfinder cells protruding from the tips of the cohorts. The absence of adhesion to fibronectin prevented the appearance of polarized pathfinders and lead to random, oscillatory motility. Our data suggest a novel role for TGF-beta in the control of collective migration of epithelial cohorts.
Binamé
Fabien
F
University of Montpellier, Centre National de la Recherche Scientifique, Institut de Génétique Moléculaire de Montpellier, 34293 Montpellier Cedex 5, France.
Lassus
Patrice
P
Hibner
Urszula
U
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D022081:Cell Surface Extensions / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000187:drug effects; D051379:Mice; D021122:Protein Subunits / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D005353:Fibronectins; D039482:Integrin alpha5; D021122:Protein Subunits; D016212:Transforming Growth Factor beta; D020830:rac1 GTP-Binding Protein