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Publication : Krüppel-like factor 5 controls keratinocyte migration via the integrin-linked kinase.

First Author  Yang Y Year  2008
Journal  J Biol Chem Volume  283
Issue  27 Pages  18812-20
PubMed ID  18450752 Mgi Jnum  J:138172
Mgi Id  MGI:3804385 Doi  10.1074/jbc.M801384200
Citation  Yang Y, et al. (2008) Kruppel-like factor 5 controls keratinocyte migration via the integrin-linked kinase. J Biol Chem 283(27):18812-20
abstractText  Migration of epithelial cells is critical for normal homeostasis in gut and skin, but the factors regulating this process are not completely understood. The zinc finger transcription factor Klf5 (IKLF; BTEB2) is highly expressed in proliferating cells of esophagus, skin, and other organs. We hypothesized that Klf5 regulates keratinocyte migration via the integrin-linked kinase (ILK), which, like Klf5, is localized to basal keratinocytes. We stably transduced mouse primary esophageal keratinocytes to overexpress Klf5 or small interfering RNA against Klf5. Klf5 overexpression in keratinocytes increased migration and correlated directly with ILK expression and activation. ILK expression restored migratory capacity in keratinocytes with suppression of Klf5, whereas ILK small interfering RNA blocked the increased migration resulting from Klf5 overexpression. By chromatin immunoprecipitation, electromobility shift assay, and luciferase reporter assays, we confirmed that ILK was a direct target for Klf5. In addition, Klf5 induced the activation of the ILK targets Cdc42 and myosin light chain, which are critical for cell migration and motility but not Rac1, AKT, or GSK3beta. Overall, these results demonstrate that Klf5 is a key regulator of cell migration via ILK and provide new insight into the regulation of epithelial cell migration.
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