Lin, Sui-WenSui-WenLinKe, Ferng-ChunFerng-ChunKeHsiao, Pei-WenPei-WenHsiaoLee, Ping-PingPing-PingLeeLee, Ming-TingMing-TingLeeHwang, Jiuan-JiuanJiuan-JiuanHwang2009-07-012018-07-062009-07-012018-07-062007http://ntur.lib.ntu.edu.tw//handle/246246/161735The present study investigated the role of integrin-linked kinase (ILK) in TGFβ1-stimulated invasion/migration of human ovarian cancer cells. We investigated TGFβ1 regulation of ILK, and effects of ILK knockdown on TGFβ1-stimulated invasion/migration and the associated proteinase systems, urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMPs) in SKOV3 cells. TGFβ1 stimulated ILK kinase activity, and had no effect on ILK protein/mRNA levels. Transient transfection of an ILK-specific siRNA (ILK-H) reduced ILK protein level, mRNA level and kinase activity. ILK knockdown by ILK-H suppressed the basal and TGFβ1-stimulated invasion and migration. Further, ILK-H reduced the basal and TGFβ1-stimulated?secretion of uPA, and increased the?secretion of its inhibitor (PAI-1). Conversely, ILK-H did not affect TGFβ1-stimulated?secretion of MMP2 and its cell-associated activator MT1-MMP. Additionally, TGFβ1 activated Smad2 phosphorylation, and this was not affected by ILK knockdown. Earlier reports indicate that Smad2 activation increased the expression of MMP2 and MT1-MMP. Thus, TGFβ1 may act through ILK-independent and Smad2-dependent signaling in regulating MMP2 and MT1-MMP in SKOV3 cells. Collectively, this study suggests that ILK serves as a key mediator in TGFβ1 regulation of uPA/PAI-1 system critical for the invasiveness of human ovarian cancer cells. And ILK is a potential target for cancer therapy. ? 2006 Elsevier Inc. All rights reserved.application/pdf1013878 bytesapplication/pdfen-USIntegrin-linked kinase (ILK); Invasion; Migration; MMP; PAI-1; SKOV3 ovarian cancer cell line; TGFβ1; uPA[SDGs]SDG3gelatinase A; integrin linked kinase; matrix metalloproteinase; messenger RNA; plasminogen activator inhibitor 1; proteinase; Smad2 protein; small interfering RNA; transforming growth factor beta1; urokinase; article; cancer cell; cancer invasion; cell invasion; cell migration; cell stimulation; controlled study; enzyme activity; enzyme regulation; enzyme release; female; human; human cell; ovary cancer; priority journal; protein expression; protein phosphorylation; protein targeting; transient transfection10.1016/j.yexcr.2006.11.003http://ntur.lib.ntu.edu.tw/bitstream/246246/161735/1/12.pdf