Krüppel-like factor 5 controls keratinocyte migration via the integrin-linked kinase.
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.
Yang
Yizeng
Y
Department of Medicine, Gastroenterology Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Tetreault
Marie-Pier
MP
Yermolina
Yuliya A
YA
Goldstein
Bree G
BG
Katz
Jonathan P
JP
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D004947:Esophagus / Q000166:cytology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D000099200:Scaffold Protein ILK
D051741:Kruppel-Like Transcription Factors; D018994:Myosin Light Chains; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D020764:cdc42 GTP-Binding Protein; D000099200:Scaffold Protein ILK; C118391:Klf5 protein, mouse