Integrin-linked protein kinase regulates fibronectin matrix assembly, E-cadherin expression, and tumorigenicity.
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 beta1 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.
Wu
C
C
Samuel C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259, USA. cwu@bmg.bhs.uab.edu
Keightley
S Y
SY
Leung-Hagesteijn
C
C
Radeva
G
G
Coppolino
M
M
Goicoechea
S
S
McDonald
J A
JA
Dedhar
S
S
D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats
D015820:Cadherins; D019012:Integrin beta1; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D011494:Protein Kinases