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Paula Reventun, Matilde Alique, Irene Cuadrado, Susana Márquez, Rocío Toro, Carlos Zaragoza, Marta Saura
OBJECTIVE: ILK (integrin-linked kinase) plays a key role in controlling vasomotor tone and is decreased in atherosclerosis. The objective of this study is to test whether nitric oxide (NO) regulates ILK in vascular remodeling. APPROACH AND RESULTS: We found a striking correlation between increased levels of inducible nitric oxide and decreased ILK levels in human atherosclerosis and in a mouse model of vascular remodeling (carotid artery ligation) comparing with iNOS (inducible NO synthase) knockout mice...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Xiang Zhuang, Mengxin Lv, Zhenyu Zhong, Luyu Zhang, Rong Jiang, Junxia Chen
BACKGROUND: Integrin-linked kinase (ILK) is a multifunctional adaptor protein which is involved with protein signalling within cells to modulate malignant (cancer) cell movement, cell cycle, metastasis and epithelial-mesenchymal transition (EMT). Our previous experiment demonstrated that ILK siRNA inhibited the growth and induced apoptosis of bladder cancer cells as well as increased the expression of Ribonuclease inhibitor (RI), an important cytoplasmic protein with many functions. We also reported that RI overexpression inhibited ILK and phosphorylation of AKT and GSK3β...
August 30, 2016: Journal of Experimental & Clinical Cancer Research: CR
Laure Fourel, Anne Valat, Eva Faurobert, Raphael Guillot, Ingrid Bourrin-Reynard, Kefeng Ren, Laurence Lafanechère, Emmanuelle Planus, Catherine Picart, Corinne Albiges-Rizo
Understanding how cells integrate multiple signaling pathways to achieve specific cell differentiation is a challenging question in cell biology. We have explored the physiological presentation of BMP-2 by using a biomaterial that harbors tunable mechanical properties to promote localized BMP-2 signaling. We show that matrix-bound BMP-2 is sufficient to induce β3 integrin-dependent C2C12 cell spreading by overriding the soft signal of the biomaterial and impacting actin organization and adhesion site dynamics...
March 14, 2016: Journal of Cell Biology
Ming-Yi Ho, Shao-Wen Hung, Chi-Ming Liang, Shu-Mei Liang
Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus binds to integrins to modulate Akt/GSK3-β signaling and suppress migration/invasion and metastasis of cancer cells, but the underlying molecular mechanism is unclear. Here, we showed that the rVP1-mediated inhibition of Akt/GSK3-β signaling and cell migration/invasion was accompanied by downregulation in phosphatidylinositol (3,4,5)-triphosphate (PIP3), integrin-linked kinase (ILK) and IKK/NF-κB signaling as well as suppression of COX-2/PGE2 and MIG-7...
June 15, 2014: Oncotarget
María Isabel Rodríguez, Andreína Peralta-Leal, Francisco O'Valle, José Manuel Rodriguez-Vargas, Ariannys Gonzalez-Flores, Jara Majuelos-Melguizo, Laura López, Santiago Serrano, Antonio García de Herreros, Juan Carlos Rodríguez-Manzaneque, Rubén Fernández, Raimundo G Del Moral, José Mariano de Almodóvar, F Javier Oliver
PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells...
June 2013: PLoS Genetics
Katharina Malinowsky, Claudia Wolff, Daniela Berg, Tibor Schuster, Axel Walch, Holger Bronger, Heiko Mannsperger, Christian Schmidt, Ulrike Korf, Heinz Höfler, Karl-Friedrich Becker
The supporting role of urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor 1 (PAI-1) in migration and invasion is well known. In addition, both factors are key components in cancer cell-related signaling. However, little information is available for uPA and PAI-1-associated signaling pathways in primary cancers and corresponding lymph node metastases. The aim of this study was to compare the expression of uPA and PAI-1-associated signaling proteins in 52 primary breast cancers and corresponding metastases...
April 2012: Translational Oncology
Joel Cerna Cortés, Eliud Alfredo Garcia Montalvo, Jesús Muñiz, Dominique Mornet, Efrain Garrido, Federico Centeno, Bulmaro Cisneros
Previously, it was shown that Dp71f binds to the beta1-integrin adhesion complex to modulate PC12 cell adhesion. The absence of Dp71f led to a failure in the beta1-integrin adhesion complex formation. One of the structural proteins which links the beta1-integrin cytoplasmic domain to the actin cytoskeleton is ILK. GSK3-beta is an ILK substrate and the carboxi-terminal region of dystrophin 427 is a substrate for hierarchical phosphorylation by GSK3-beta. Dp71f contains the carboxi-terminal domain present in dystrophin 427...
March 2009: Neurochemical Research
Carsten Grashoff, Attila Aszódi, Takao Sakai, Ernst B Hunziker, Reinhard Fässler
The interaction of chondrocytes with the extracellular-matrix environment is mediated mainly by integrins. Ligated integrins are recruited to focal adhesions (FAs) together with scaffolding proteins and kinases, such as integrin-linked kinase (Ilk). Ilk binds the cytoplasmic domain of beta1-, beta2- and beta3-integrins and recruits adaptors and kinases, and is thought to stimulate downstream signalling events through phosphorylation of protein kinase B/Akt (Pkb/Akt) and glycogen synthase kinase 3-beta (GSK3-beta)...
April 2003: EMBO Reports
A Novak, S Dedhar
Beta-catenin plays a structural role in cell adhesion by binding to cadherins at the intracellular surface of the plasma membrane and a signaling role in the cytoplasm as the penultimate downstream mediator of the wnt signaling pathway. The ultimate mediator of this pathway is a nuclear complex of beta-catenin acting as a coactivtor with lymphoid enhancer factor/T cell factor (Lef/Tcf) transcription factors to stimulate transcription of a variety of target genes. Signaling through beta-catenin is regulated by modulating its degradation and nuclear translocation...
October 30, 1999: Cellular and Molecular Life Sciences: CMLS
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