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Integrin linked kinase

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https://www.readbyqxmd.com/read/28794235/integrin-linked-kinase-expression-in-myeloid-cells-promotes-inflammatory-signaling-during-experimental-colitis
#1
Afsar U Ahmed, Howard C H Yim, Mariah Alorro, Matthias Ernst, Bryan R G Williams
The pathology of inflammatory bowel diseases is driven by the inflammatory signaling pathways associated with mucosal epithelial damage. Myeloid cells are known to play an essential role in mediating epithelial inflammatory responses during injury. However, the precise role of these cells in stimulating intestinal inflammation and the subsequent tissue damage is unclear. In this article, we show that expression of integrin-linked kinase (ILK) in myeloid cells is critical for the epithelial inflammatory signaling during colitis induced by dextran sodium sulfate...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28791358/ilk-promotes-cell-proliferation-in-breast-cancer-cells-by-activating-the-pi3k-akt-pathway
#2
Yikun Qu, Chunfang Hao, Jian Xu, Zhuoxin Cheng, Weiqun Wang, Hong Liu
Breast cancer is a very common malignant tumor, whose incidence ranks the first among various types of cancer in women worldwide. An important hallmark of cancer is the activation of oncogenes, which lead to overgrowth of cancer cells. Therefore, it is necessary to identify the critical genes involved in regulating the progression of breast cancer and elucidate the corresponding molecular mechanisms. The present study demonstrated that integrin‑linked kinase (ILK) overexpression promoted cell proliferation and growth in MCF‑7 cells, while ILK knockdown led to growth arrest in MDA‑MB‑231 cells...
August 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28790850/emodin-suppresses-proliferation-migration-and-invasion-in-ovarian-cancer-cells-by-down-regulating-ilk-in-vitro-and-in-vivo
#3
Jingjing Lu, Ying Xu, Zhe Zhao, Xiaoning Ke, Xuan Wei, Jia Kang, Xuan Zong, Hongluan Mao, Peishu Liu
OBJECTIVE: Although our previous studies have confirmed that 1, 3, 8-trihydroxy-6-methylant hraquinone (emodin) inhibits migration and invasion in epithelial ovarian cancer (EOC) cells, the underlying molecular mechanism remains unknown. Here, the aim was to investigate the effects of emodin on EOC cells and to study further the mechanism underlying this process, both in vitro and in vivo. MATERIALS AND METHODS: Cell proliferation was evaluated by the methylthiazolyl tetrazolium assay...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28783171/the-pdgfr%C3%AE-laminin-b1-keratin-19-cascade-drives-tumor-progression-at-the-invasive-front-of-human-hepatocellular-carcinoma
#4
O Govaere, M Petz, J Wouters, Y-P Vandewynckel, E J Scott, B Topal, F Nevens, C Verslype, Q M Anstee, H Van Vlierberghe, W Mikulits, T Roskams
Human hepatocellular carcinomas (HCCs) expressing the biliary/hepatic progenitor cell marker keratin 19 (K19) have been linked with a poor prognosis and exhibit an increase in platelet-derived growth factor receptor α (PDGFRα) and laminin beta 1 (LAMB1) expression. PDGFRα has been reported to induce de novo synthesis of LAMB1 protein in a Sjogren syndrome antigen B (La/SSB)-dependent manner in a murine metastasis model. However, the role of this cascade in human HCC remains unclear. This study focused on the functional role of the PDGFRα-La/SSB-LAMB1 pathway and its molecular link to K19 expression in human HCC...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28780796/-changes-of-integrin-linked-kinase-expression-on-rats-pulmonary-fibrosis-induced-by-paraquat
#5
Y W Su, Y H Li, F Li, Y C Feng, H Huang, B X Wei, Y M Liu
Objective: To observe the expression of integrin-linked kinase on pulmonary fibrosis of paraquat (PQ) poisoning rats, and to discuss the relationship between ILK with pulmonary fibrosis induced by paraquat. Methods: Forty male Sprague-Dawley (SD) rats were randomly divided into control group and paraquat group, 20 in each group; the PQ group rats were intraperitoneally injected PQ liquid (18 mg/kg) , and the control group rats were injected the same volume of saline; 5 rats of these two groups were respectively sacrificed after 7, 14, 28, 56 days of PQ injection; according to the results of lung biopsy HE staining and Masson staining to observe the lung pathologic changes, measure the value of lung hydroxyproline and the expression of ILK...
May 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/28768233/identification-of-transcriptome-signature-for-myocardial-reductive-stress
#6
Justin M Quiles, Madhusudhanan Narasimhan, Timothy Mosbruger, Gobinath Shanmugam, David Crossman, Namakkal S Rajasekaran
The nuclear factor erythroid 2 like 2 (Nfe2l2/Nrf2) is a master regulator of antioxidant gene transcription. We recently identified that constitutive activation of Nrf2 (CaNrf2) caused reductive stress (RS) in the myocardium. Here we investigate how chronic Nrf2 activation alters myocardial mRNA transcriptome in the hearts of CaNrf2 transgenic (TG-low and TG-high) mice using an unbiased integrated systems approach and next generation RNA sequencing followed by qRT-PCR methods. A total of 246 and 1031 differentially expressed genes (DEGs) were identified in the heart of TGL and TGH in relation to NTG littermates at ~ 6 months of age...
July 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28736155/integrin-linked-kinase-regulates-the-transcription-of-aqp2-by-nfatc3
#7
Marco Hatem-Vaquero, Mercedes Griera, Wieslawa Giermakowska, Alicia Luengo, Laura Calleros, Laura V Gonzalez Bosc, Diego Rodríguez-Puyol, Manuel Rodríguez-Puyol, Sergio De Frutos
Two processes are associated with progressive loss of renal function: 1) decreased aquaporin-2 (AQP2) expression and urinary concentrating capacity (Nephrogenic Diabetes Insipidus, NDI); and 2) changes in extracellular matrix (ECM) composition, e.g. increased collagen I (Col I) deposition, characteristic of tubule-interstitial fibrosis. AQP2 expression is regulated by both the ECM-to-intracellular scaffold protein integrin-linked kinase (ILK) by NFATc/AP1 and other transcription factors. In the present work, we used in vivo and in vitro approaches to examine ILK participation in NFATc3/AP-1-mediated increases in AQP2 gene expression...
July 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28700332/overexpression-of-stathmin-plays-a-pivotal-role-in-the-metastasis-of-esophageal-squamous-cell-carcinoma
#8
Gaijing Han, Zongyong Wu, Nan Zhao, Lanping Zhou, Fang Liu, Fangfei Niu, Yang Xu, Xiaohang Zhao
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is a serious malignant tumor that affects human health. We analyzed the correlation between serum stathmin level and ESCC and elucidated the molecular mechanisms of stathmin's promotion of ESCC cell invasion and metastasis. METHODS: Stathmin level in ESCC and healthy control serum were detected by enzyme-linked immunosorbent assay (ELISA), and the clinical parameters were analyzed. We established ESCC cells with stathmin overexpression or knockdown and then evaluated the effects of stathmin on invasion and metastasis in ESCC...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699640/lfa-1-activates-focal-adhesion-kinases-fak1-pyk2-to-generate-lat-grb2-skap1-complexes-that-terminate-t-cell-conjugate-formation
#9
Monika Raab, Yuning Lu, Karsten Kohler, Xin Smith, Klaus Strebhardt, Christopher E Rudd
Lymphocyte function-associated antigen 1 (LFA-1) affinity and avidity changes have been assumed to mediate adhesion to intercellular adhesion molecule-1 for T-cell conjugation to dendritic cells (DC). Although the T-cell receptor (TCR) and LFA-1 can generate intracellular signals, the immune cell adaptor protein linker for the activation of T cells (LAT) couples the TCR to downstream events. Here, we show that LFA-1 can mediate both adhesion and de-adhesion, dependent on receptor clustering. Although increased affinity mediates adhesion, LFA-1 cross-linking induced the association and activation of the protein-tyrosine kinases FAK1/PYK1 that phosphorylated LAT selectively on a single Y-171 site for the binding to adaptor complex GRB-2-SKAP1...
July 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28698049/tensins-bridging-amp-activated-protein-kinase-with-integrin-activation
#10
REVIEW
Maria Georgiadou, Johanna Ivaska
Integrin activation is essential for cell adhesion and for connecting the extracellular matrix to the actin cytoskeleton. Thus, inappropriate integrin activation has been linked to several diseases, including cancer. Recent insights demonstrate that the main fibrillar adhesion component tensin maintains β1-integrin active in these mature adhesions. Depletion or silencing of AMP-activated protein kinase (AMPK), the energy sensor involved in maintaining the energy balance of the cell, enhances integrin activity by increasing the expression of tensin and thereby promoting cell adhesion, matrix formation, and mechanotransduction...
July 8, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28697798/a-proteomic-analysis-of-lrrk2-binding-partners-reveals-interactions-with-multiple-signaling-components-of-the-wnt-pcp-pathway
#11
Alena Salašová, Chika Yokota, David Potěšil, Zbyněk Zdráhal, Vítězslav Bryja, Ernest Arenas
BACKGROUND: Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients...
July 11, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28692035/role-of-integrin-linked-kinase-in-regulating-the-protein-stability-of-the-muc1-c-oncoprotein-in-pancreatic-cancer-cells
#12
H-L Huang, H-Y Wu, P-C Chu, I-L Lai, P-H Huang, S K Kulp, S-L Pan, C-M Teng, C-S Chen
MUC1-C overexpression has been associated with the progression of pancreatic tumors by promoting the aggressive and metastatic phenotypes. As MUC1 is a STAT3 target gene, STAT3 plays a major role in regulating MUC1-C expression. In this study, we report an alternative mechanism by which integrin-linked kinase (ILK) post-transcriptionally modulates the expression of MUC1-C by maintaining its protein stability in pancreatic cancer cells. We found that ILK acts in concert with STAT3 to facilitate IL-6-mediated upregulation of MUC1-C; ILK depletion was equally effective as STAT3 depletion in abolishing IL-6-induced MUC1-C overexpression without disturbing the phosphorylation or cellular distribution of STAT3...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28669853/effect-of-sirolimus-on-arteriosclerosis-induced-by-advanced-glycation-end-products-via-inhibition-of-the-ilk-mtor-pathway-in-kidney-transplantation-recipients
#13
Zhen Xu, Xuzhong Liu, Zijie Wang, Jun Tao, Zhijian Han, Min Gu, Wei Zhang, Ruoyun Tan
To investigate the effect and related mechanism of sirolimus (SRL) in arteriosclerosis(AS) induced by advanced glycation end products (AGEs) in kidney transplantation recipients (KTRs).Human kidney tissues from KTRs before and after treatment with SRL were assessed by hematoxylin-eosin and immunohistochemical staining. Rat vascular smooth muscle cells (VSMCs) were treated with AGEs and/or SRL. The expressions of α-smooth muscle actin (α-SMA), osteopontin (OPN), actinin-associated LIM protein (ALP), proliferating cell nuclear antigen (PCNA), integrin-linked kinase (ILK) and the mTOR signaling pathway proteins were examined using western blot assay...
June 29, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28663280/megakaryocytic-smad4-regulates-platelet-function-through-syk-and-rock2-expression
#14
Yanhua Wang, Lirong Jiang, Xi Mo, Yu Lan, Xiao Yang, Xinyi Liu, Jian Zhang, Li Zhu, Junling Liu, Xiaolin Wu
Smad4, a key transcription factor in the TGF-β signaling pathway, is involved in a variety of cell physiological and pathological processes. Here, we characterized megakaryocyte/platelet-specific Smad4 deficiency in mice to elucidate its effect on platelet function. We found that megakaryocyte/platelet-specific loss of Smad4 caused mild thrombocytopenia and significantly extended first occlusion time and tail bleeding time in mice. Smad4-deficient platelets showed reduced agonist-induced platelet aggregation...
June 29, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28651423/-advances-in-the-research-of-role-of-integrin-linked-kinase-in-angiogenesis
#15
W B Zhou, Y Y Li
Integrin-linked kinase (ILK) has been found for twenty years, and its biological characteristics have been extensively studied by multi-discipline. At present, studies of ILK are mainly focused on its roles in angiogenesis, tumor formation, and tissue fibrosis, etc. In recent years, the regulation effect of ILK in angiogenesis attracts attention of researchers. The studies showed that ILK can stimulate the secretion of angiogenic factor, promote the proliferation and migration of endothelial cells and inhibit their apoptosis, and therefore play an important role in the regulation of angiogenesis...
May 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28630423/thymosin-beta-4-regulates-activation-of-hepatic-stellate-cells-via-hedgehog-signaling
#16
Jieun Kim, Jeongeun Hyun, Sihyung Wang, Chanbin Lee, Jae-Wook Lee, Eun-Yi Moon, Heejae Cha, Anna Mae Diehl, Youngmi Jung
The molecular mechanisms of thymosin beta-4 (TB4) involved in regulating hepatic stellate cell (HSC) functions remain unclear. Therefore, we hypothesize that TB4 influences HSC activation through hedgehog (Hh) pathway. HSC functions declined in a TB4 siRNA-treated LX-2. TB4 suppression down-regulated both integrin linked kinase (ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase 3 beta (pGSK-3B), an inactive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoothened and GLI2...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615322/in-vivo-manipulation-of-the-extracellular-matrix-induces-vascular-regression-in-a-basal-chordate
#17
Delany Rodriguez, Brian P Braden, Scott W Boyer, Daryl A Taketa, Leah Setar, Chris Calhoun, Alessandro Di Maio, Adam Langenbacher, Megan T Valentine, Anthony W De Tomaso
We investigated the physical role of the extracellular matrix (ECM) in vascular homeostasis in the basal chordate Botryllus schlosseri, which has a large, transparent, extracorporeal vascular network encompassing an area >100 cm(2) We found that the collagen cross-linking enzyme lysyl oxidase is expressed in all vascular cells and that in vivo inhibition using β-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 h. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose dependent...
July 7, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28578803/head-and-neck-cancer-cell-radiosensitization-upon-dual-targeting-of-c-abl-and-beta1-integrin
#18
Philipp Koppenhagen, Ellen Dickreuter, Nils Cordes
Integrin-mediated cell adhesion to extracellular matrix (ECM) critically contributes to cancer cell therapy resistance and DNA double strand break (DSB) repair. c-Abl tyrosine kinase has been linked to both of these processes. Based on our previous findings indicating c-Abl hyperphosphorylation on tyrosine (Y) 412 and threonine (T) 735 upon beta1-integrin inhibition, we hypothesized c-Abl tyrosine kinase as an important mediator of beta1-integrin signaling for radioresistance. In a panel of 8 cell lines from different solid cancer types grown in 3D laminin-rich ECM cultures, we targeted beta1 integrin with AIIB2 (mAb) and c-Abl with Imatinib with and without X-ray irradiation and subsequently examined clonogenic survival, residual DSBs, protein expression and phosphorylation...
May 31, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28577299/upa-upar-system-activation-drives-a-glycolytic-phenotype-in-melanoma-cells
#19
Anna Laurenzana, Anastasia Chillà, Cristina Luciani, Silvia Peppicelli, Alessio Biagioni, Francesca Bianchini, Elena Tenedini, Eugenio Torre, Alessandra Mocali, Lido Calorini, Francesca Margheri, Gabriella Fibbi, Mario Del Rosso
In this manuscript, we show the involvement of the uPA/uPAR system in the regulation of aerobic glycolysis of melanoma cells. uPAR over-expression in human melanoma cells controls an invasive and glycolytic phenotype in normoxic conditions. uPAR down-regulation by siRNA or its uncoupling from integrins, and hence from integrin-linked tyrosine kinase receptors (IL-TKRs), by an antagonist peptide induced a striking inhibition of the PI3K/AKT/mTOR/HIF1α pathway, resulting into impairment of glucose uptake, decrease of several glycolytic enzymes and of PKM2, a checkpoint that controls metabolism of cancer cells...
June 2, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28576970/low-intensity-pulsed-ultrasound-promotes-cell-motility-through-vinculin-controlled-rac1-gtpase-activity
#20
Paul Atherton, Franziska Lausecker, Andrew Harrison, Christoph Ballestrem
Low-intensity pulsed ultrasound (LIPUS) is a therapy used clinically to promote healing. Using live-cell imaging we show that LIPUS stimulation, acting through integrin-mediated cell-matrix adhesions, rapidly induces Rac1 activation associated with dramatic actin cytoskeleton rearrangements. Our study demonstrates that the mechanosensitive focal adhesion (FA) protein vinculin, and both focal adhesion kinase (FAK, also known as PTK2) and Rab5 (both the Rab5a and Rab5b isoforms) have key roles in regulating these effects...
July 15, 2017: Journal of Cell Science
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