However, the role of keratins for biomechanical properties and invasion of epithelial cells are only partially understood. Here, we address this issue in murine keratinocytes lacking all keratins upon genome engineering. In contrast to prediction, keratin-free cells show an about 60% higher cell deformability even for small deformations. This is compared to less pronounced softening effects for actin depolymerization induced via latrunculin A. To relate these findings with functional consequences, we use invasion and three-dimensional growth assays. These reveal higher invasiveness of keratin-free cells. Re-expression of a small amount of the keratin pair K5/ K14 in keratin-free cells reverses the above phenotype for the invasion but does not with respect to cell deformability. Our data shows a novel role of keratins as major player of cell stiffness influencing invasion with implications for epidermal homeostasis and pathogenesis. This study supports the view that downregulation of keratins observed during epithelial-mesenchymal transition directly contributes to the migratory and invasive behavior of tumor cells. (see K. Seltmann et al., PNAS, in press).
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