Transforming growth factor beta controls the directional migration of hepatocyte cohorts by modulating their adhesion to fibronectin

Biname, F.; Lassus, P.; Hibner, U.

Mol Biol Cell

2008-03 / vol 19 / pages 945-56


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.

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Humans; Animals; Mice; Gene Expression Profiling; Cell Line; Protein Subunits/metabolism; Apoptosis/drug effects; Gene Expression Regulation/drug effects; rac1 GTP-Binding Protein/metabolism; Cell Movement/*drug effects; Cell Adhesion/drug effects; Cell Communication/drug effects; Cell Membrane/drug effects/metabolism; Cell Surface Extensions/drug effects/metabolism; Epithelium/drug effects; Fibronectins/*metabolism; Hepatocytes/*cytology/*drug effects/metabolism; Integrin alpha5/genetics/metabolism; Mesoderm/drug effects; Transforming Growth Factor beta/*pharmacology

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