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| Poster, Friday, 19:00 |
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| Keratin-mediated repression
of cell migration
Kerstin Seltmann
University of Leipzig, Germany |
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| Contact:
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Migration is an essential process in the skin, where it participates in
skin development, wound healing, inflammation and malignant progression.
In contrast to the well established role of actin and microtubules, the
contribution of the keratin cytoskeleton in migration is not well understood.
Keratins build up intermediate filaments in all epithelial cells and interact
with cell-cell and cell-matrix contacts. The latter mediate the cross-talk
of the cytoskeleton with the extracellular matrix and therefore play a
crucial role in migration. Thus, to address for the first time the function
of the keratin cytoskeleton in dynamic processes like cell migration, we
generated a keratin-free cell culture model from knockout mice [Vijayaraj
et al., 2009].
Here, we report that the loss of the keratin cytoskeleton enhances
the migration of keratinocytes. Re-expression of a single keratin pair
reverted this behaviour, demonstrating keratin-dependence. Moreover, we
found that altered migration coincided with altered distribution of plectin
and beta4-integrin. Unexpectedly, the localisation of actin-dependent focal
adhesions was altered as well.
Our data support a model by which keratins directly stabilize hemidesmosomes
through maintaining the plectin-beta4-integrin linkage and indirectly stabilize
focal adhesions through unknown mechanisms. These results support the view
that the downregulation of keratins observed during epithelial-mesenchymal
transition supports the migratory and invasive behaviour of tumour cells. |
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