Fibronectin (Fn) matrix plays important roles in many biological processes including morphogenesis and tumorigenesis. Recent studies have demonstrated a critical role of integrin cytoplasmic domains in regulating Fn matrix assembly, implying that intracellular integrin-binding proteins may be involved in controlling extracellular Fn matrix assembly. We report here that overexpression of integrin-linked kinase (ILK), a newly identified serine/threonine kinase that binds to the integrin β1 cytoplasmic domain, dramatically stimulated Fn matrix assembly in epithelial cells. The integrin- linked kinase activity is involved in transducing signals leading to the up- regulation of Fn matrix assembly, as overexpression of a kinase-inactive ILK mutant failed to enhance the matrix assembly. Moreover, the increase in Fn matrix assembly induced by ILK overexpression was accompanied by a substantial reduction in the cellular E-cadherin. Finally, we show that ILK- overexpressing epithelial cells readily formed tumors in nude mice, despite forming an extensive Fn matrix. These results identify ILK as an important regulator of pericellular Fn matrix assembly, and suggest a novel critical role of this integrin-linked kinase in cell growth, cell survival, and tumorigenesis.
CITATION STYLE
Wu, C., Keightley, S. Y., Leung-Hagesteijn, C., Radeva, G., Coppolino, M., Goicoechea, S., … Dedhar, S. (1998). Integrin-linked protein kinase regulates fibronectin matrix assembly, E- cadherin expression, and tumorigenicity. Journal of Biological Chemistry, 273(1), 528–536. https://doi.org/10.1074/jbc.273.1.528
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