Keratin network dynamics in three different situations. (A) Approaching epithelial cells, e.g., upon wound closure: The motile cells require a dynamic cytoskeleton. This is supported by the keratin cycle, which allows rapid turnover and restructuring of the peripheral network using focal adhesion–dependent guidance cues, whereas the perinuclear network remains comparatively static. ecm, extracellular matrix; fa, focal adhesion; n, nucleus. (B) Differentiated static epithelium: Upon stable contact formation with neighboring epithelial cells through tight junctions (tj), adherens junctions (aj), and desmosomes (des), and with the extracellular matrix of the basement membrane through hemidesmosomes (hdes), the keratin network matures into topologically restricted thick bundles with very little keratin cycling. (C) Invasion of epithelial cell into connective tissue: Cells lose contact with each other and reduce stable hemidesmosomal adhesion coincident with up-regulation of keratin cycling in the leading edge for network remodeling.