INTEGRIN-INDUCED PROTEIN-KINASE REGULATES FIBRONECTIN MATRIX ASSEMBLY, E-CADHERIN EXPRESSION, AND TUMORIGENICITY

Fibronectin (Fn) matrix plays important roles in many biological proce sses including morphogenesis and tumorigenesis. Recent studies have de monstrated a critical role of integrin cytoplasmic domains in regulati ng Fn matrix assembly, implying that intracellular integrin-binding pr oteins 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 beta(1) 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 assem bly, as overexpression of a kinase-inactive ILK mutant failed to enhan ce the matrix assembly, Moreover, the increase in Fn matrix assembly i nduced by ILK overexpression was accompanied by a substantial reductio n 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 reg ulator of pericellular Fn matrix assembly, and suggest a novel critica l role of this integrin-linked kinase in cell growth, cell survival, a nd tumorigenesis.