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Integrin linked kinase

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https://www.readbyqxmd.com/read/29679656/pd-1-blocks-lytic-granule-polarization-with-concomitant-impairment-of-integrin-outside-in-signaling-in-natural-killer-cell-immunological-synapse
#1
Yu Huang, Zhiying Chen, Joon Hee Jang, Mirza S Baig, Grant Bertolet, Casey Schroeder, Shengjian Huang, Qian Hu, Yong Zhao, Dorothy E Lewis, Lidong Qin, Michael Xi Zhu, Dongfang Liu
BACKGROUND: Inhibitory receptor programmed cell death protein-1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic virus infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. OBJECTIVE: We sought to determine what effect PD-1 signaling has on NK cells...
April 18, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29656700/hif-2%C3%AE-ilk-is-involved-in-mesenchymal-stromal-cell-angiogenesis-in-multiple-myeloma-under-hypoxic-conditions
#2
Xiaoying Zhang, Yinhui Xu, Hongbo Liu, Pan Zhao, Yafang Chen, Zhijie Yue, Zhiqing Zhang, Xiaofang Wang
Mesenchymal stromal cells are proven to be likely induce the angiogenic response in multiple myeloma and thus represent an enticing target for antiangiogenesis therapies for multiple myeloma. Substantial evidence indicates that angiogenesis in multiple myeloma is complex and involves direct production of angiogenic cytokines by abnormal plasma cells and these B-cell neoplasia generated pathophysiology change within the microenvironment. In this study, we demonstrated that mesenchymal stromal cells cultured with U266/Lp-1 under hypoxic conditions resulted in an increased α-smooth muscle actin expression and high productive levels of both hypoxia-inducible factor-2α and integrin-linked kinase proteins...
January 1, 2018: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29611449/splenic-tyrosine-kinase-syk-inhibitors-and-their-possible-use-in-acute-myeloid-leukemia
#3
Sushma Bartaula-Brevik, Marte Karen Lindstad Brattås, Tor Henrik Anderson Tvedt, Håkon Reikvam, Øystein Bruserud
Splenic tyrosine kinase (SYK) is a non-receptor tyrosine kinase. It is important for downstream signaling from several cell surface receptors, including Fc receptors, complement receptors and integrins. SYK can have either oncogenic or tumor suppressor activity in human malignancies. Recent studies suggest that SYK inhibition may have an antileukemic effect in human acute myeloid leukemia (AML). Areas covered: Relevant publications were identified through literature searches in the PubMed database. We searched for (i) original articles describing the results from clinical studies of SYK inhibition; (ii) published articles describing the importance of SYK in human malignancies, especially AML...
April 4, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29610861/integrin-linked-kinase-controls-choroidal-neovascularization-by-recruitment-of-endothelial-progenitor-cells
#4
Xiu-Mei Yang, Chun-Guang Duan, Jian Zhang, Xiao-Jie Qu, Yu-Sheng Wang
Purpose: Vasculogenesis has been shown to contribute to the formation of choroidal neovascularization (CNV). However, the mechanism behind the recruitment of endothelial progenitor cells (EPC) to CNV is not well understood. Therefore, we were interested to know whether integrin-linked kinase (ILK) plays a role in recruiting EPC to CNV, and its possible mechanism. Methods: We investigated the effect of hypoxia on retinal pigment epithelium (RPE) cells expressing ILK, hypoxia-inducible factor 1α (HIF-1α), stromal-derived factor-1 (SDF-1), and vascular endothelial growth factor (VEGF), and we further examined the effect of ILK small interfering RNA (siRNA) on their expression...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29610281/adaptive-resistance-to-chemotherapy-a-multi-fak-torial-linkage
#5
EDITORIAL
Kristin N Taylor, David D Schlaepfer
Oncogenes provide tumor cells with a growth and survival advantage. Directed therapies targeted to oncogenic mutations (such as BRAF V600E) are part of effective late-stage melanoma treatment. However, tumors with BRAF V600E mutations, in approximately 10% of colorectal cancer, are generally treatment-insensitive. Research has identified various "feedback" mechanisms that result in BRAF signal pathway reactivation in response to BRAF inhibition. Herein, we highlight key findings from Chen and colleagues (this issue) showing that integrin-associated focal adhesion kinase (FAK) activation selectively occurs in BRAF V600E-mutant colorectal cancer cells in response to pharmacological BRAF inhibition...
April 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29608014/expression-of-emt-inducers-integrin-linked-kinase-ilk-and-zeb1-in-phyllodes-breast-tumors-is-associated-with-aggressive-phenotype
#6
Ioanna Akrida, Sofia Nikou, Konstantinos Gyftopoulos, Marianna Argentou, Sofia Kounelis, Vassiliki Zolota, Vasiliki Bravou, Helen Papadaki
Phyllodes tumors (PTs) of the breast constitute an uncommon group of mammary fibroepithelial lesions with ambiguous biologic behavior. Recent evidence suggests that epithelial mesenchymal transition (EMT), a driving force of cancer progression is implicated in PTs pathogenesis. Integrin-linked kinase (ILK), a focal adhesion kinase, has been implicated in cancer and EMT and represents a novel cancer therapeutic target. In this study, we aimed to investigate ILK and EMT markers expression in phyllodes breast tumors in relation to tumor grade...
April 2, 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/29588395/substratum-stiffness-tunes-proliferation-downstream-of-wnt3a-in-part-by-regulating-integrin-linked-kinase-and-frizzled-1
#7
Siyang Han, Mei-Fong Pang, Celeste M Nelson
The Wnt/β-catenin pathway controls a variety of cellular behaviors, aberrant activation of which are associated with tumor progression in several types of cancer. The same cellular behaviors are also affected by the mechanical properties of the extracellular matrix (ECM) substratum, which induces signaling through integrins and integrin-linked kinase (ILK). Here, we examined the role of substratum stiffness in the regulation of cell proliferation downstream of Wnt3a. We found that treatment with Wnt3a increased proliferation of cells cultured on stiff substrata, with compliances characteristic of breast tumors, but not of cells on soft substrata, with compliances comparable to that of normal mammary tissue...
March 27, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29568383/protective-role-of-integrin-linked-kinase-against-oxidative-stress-and-in-maintenance-of-genomic-integrity
#8
Michelle Im, Lina Dagnino
The balance between the production of reactive oxygen species and activation of antioxidant pathways is essential to maintain a normal redox state in all tissues. Oxidative stress caused by excessive oxidant species generation can cause damage to DNA and other macromolecules, affecting cell function and viability. Here we show that integrin-linked kinase (ILK) plays a key role in eliciting a protective response to oxidative damage in epidermal cells. Inactivation of the Ilk gene causes elevated levels of intracellular oxidant species (IOS) and DNA damage in the absence of exogenous oxidative insults...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29540687/compression-force-sensing-regulates-integrin-%C3%AE-iib-%C3%AE-3-adhesive-function-on-diabetic-platelets
#9
Lining Ju, James D McFadyen, Saheb Al-Daher, Imala Alwis, Yunfeng Chen, Lotte L Tønnesen, Sophie Maiocchi, Brianna Coulter, Anna C Calkin, Eric I Felner, Neale Cohen, Yuping Yuan, Simone M Schoenwaelder, Mark E Cooper, Cheng Zhu, Shaun P Jackson
Diabetes is associated with an exaggerated platelet thrombotic response at sites of vascular injury. Biomechanical forces regulate platelet activation, although the impact of diabetes on this process remains ill-defined. Using a biomembrane force probe (BFP), we demonstrate that compressive force activates integrin αIIb β3 on discoid diabetic platelets, increasing its association rate with immobilized fibrinogen. This compressive force-induced integrin activation is calcium and PI 3-kinase dependent, resulting in enhanced integrin affinity maturation and exaggerated shear-dependent platelet adhesion...
March 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29533735/space-microgravity-drives-transdifferentiation-of-human-bone-marrow-derived-mesenchymal-stem-cells-from-osteogenesis-to-adipogenesis
#10
Cui Zhang, Liang Li, Yuanda Jiang, Cuicui Wang, Baoming Geng, Yanqiu Wang, Jianling Chen, Fei Liu, Peng Qiu, Guangjie Zhai, Ping Chen, Renfu Quan, Jinfu Wang
Bone formation is linked with osteogenic differentiation of mesenchymal stem cells (MSCs) in the bone marrow. Microgravity in spaceflight is known to reduce bone formation. In this study, we used a real microgravity environment of the SJ-10 Recoverable Scientific Satellite to examine the effects of space microgravity on the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs). hMSCs were induced toward osteogenic differentiation for 2 and 7 d in a cell culture device mounted on the SJ-10 Satellite...
March 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29528115/a-role-for-focal-adhesion-kinase-in-facilitating-the-contractile-responses-of-murine-gastric-fundus-smooth-muscles
#11
Yeming Xie, Koon Hee Han, Nathan Grainger, Wen Li, Robert D Corrigan, Brian A Perrino
Smooth muscle contraction involves regulating myosin light chain phosphorylation and dephosphorylation by myosin light chain kinase and myosin light chain phosphatase. CPI-17 and MYPT1 are crucial for regulating gastrointestinal smooth muscle contraction by inhibiting myosin light chain phosphatase. Integrin signalling involves the dynamic recruitment of several proteins, including FAK, to focal adhesions. FAK tyrosine kinase activation is involved in cell adhesion to the extracellular matrix via integrin signalling...
March 12, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29507698/superquant-assisted-comparative-proteome-analysis-of-glioblastoma-subpopulations-allows-for-identification-of-potential-novel-therapeutic-targets-and-cell-markers
#12
Thiago Verano-Braga, Vladimir Gorshkov, Sune Munthe, Mia D Sørensen, Bjarne W Kristensen, Frank Kjeldsen
Glioblastoma (GBM) is a highly aggressive brain cancer with poor prognosis and low survival rate. Invasive cancer stem-like cells (CSCs) are responsible for tumor recurrence because they escape current treatments. Our main goal was to study the proteome of three GBM subpopulations to identify key molecules behind GBM cell phenotypes and potential cell markers for migrating cells. We used SuperQuant-an enhanced quantitative proteome approach-to increase proteome coverage. We found 148 proteins differentially regulated in migrating CSCs and 199 proteins differentially regulated in differentiated cells...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29496692/ilk-expression-in-colorectal-cancer-is-associated-with-emt-cancer-stem-cell-markers-and-chemoresistance
#13
Dimitrios Tsoumas, Sofia Nikou, Efstathia Giannopoulou, Spyridon Champeris Tsaniras, Chaido Sirinian, Ioannis Maroulis, Stavros Taraviras, Vassiliki Zolota, Haralabos P Kalofonos, Vasiliki Bravou
BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) are critically implicated in cancer metastasis and chemoresistance. Herein, we investigated integrin-linked kinase (ILK)'s role in human colon cancer (CRC) progression and chemoresistance in relation to EMT and CSC markers. PATIENTS AND METHODS: Expression of ILK, EMT and CSC markers were evaluated by immunohistochemistry in 149 CRC samples. We also generated colon cancer cells resistant to 5-FU and oxaliplatin and studied the effect of ILK inhibition on drug response by MTT assay and on EMT and CSC markers' expression...
March 2018: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29487179/epidermal-growth-factor-receptor-and-integrins-control-force-dependent-vinculin-recruitment-to-e-cadherin-junctions
#14
Poonam Sehgal, Xinyu Kong, Jun Wu, Raimon Sunyer, Xavier Trepat, Deborah Leckband
This study reports novel findings that link E-Cadherin-mediated force-transduction signaling to vinculin targeting to intercellular junctions via epidermal growth factor receptor (EGFR) and integrins. These results build on previous findings, which demonstrated that mechanically perturbed E-Cadherin receptors activate phosphoinositide-3-kinase and downstream integrins, in an EGFR-dependent manner. Results of this study show that this EGFR-mediated kinase cascade controls the force-dependent recruitment of vinculin to stressed E-Cadherin complexes--a key early signature of cadherin-based mechanotransduction...
February 27, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29440271/phosphorylated-immunoreceptor-tyrosine-based-activation-motifs-and-integrin-cytoplasmic-domains-activate-spleen-tyrosine-kinase-via-distinct-mechanisms
#15
Lina Antenucci, Vesa P Hytönen, Jari Ylänne
Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated Immunoreceptor Tyrosine-based Activation Motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues...
February 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29436600/adenovirus-mediated-p311-ameliorates-renal-fibrosis-through-inhibition-of-epithelial-mesenchymal-transition-via-tgf-%C3%AE-1-smad-ilk-pathway-in-unilateral-ureteral-obstruction-rats
#16
Fang-Hua Qi, Ping-Ping Cai, Xiang Liu, Guo-Min Si
Epithelial-mesenchymal transition (EMT) is a critical step and key factor during renal fibrosis. Preventing renal tubular EMT is important for delaying the progression of chronic kidney disease (CKD). P311, a highly conserved 8-kDa intracellular protein, has been indicated as an important factor in myofibroblast transformation and in the progression of fibrosis. However, the related studies on P311 on renal fibrosis are limited and the mechanisms of P311 in the progression of renal tubulointerstitial fibrosis remain largely unknown...
February 12, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29379038/cardiac-shock-wave-therapy-promotes-arteriogenesis-of-coronary-micrangium-and-ilk-is-involved-in-the-biomechanical-effects-by-proteomic-analysis
#17
Wenhui Yang, Yan He, Lulu Gan, Fan Zhang, Baotong Hua, Ping Yang, Juan Liu, Li Yang, Tao Guo
Cardiac Shock Wave Therapy (CSWT) improves myocardial perfusion and ameliorates cardiac remodeling after acute myocardial infarction (AMI), but the precise mechanisms remain obscure. Herein, we have applied CSWT to a rat model of AMI to demonstrate the arteriogenesis of coronary micrangium and protein expression changes in ischemic myocardium after CSWT. Four weeks after CSWT, the fraction shortening of rats was improved greatly and the cardiomyocyte apoptosis index was significantly lower than the AMI group (P < 0...
January 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29337188/abrogation-of-fam20c-altered-cell-behaviors-and-bmp-signaling-of-immortalized-dental-mesenchymal-cells
#18
Chao Liu, Nan Zhou, Yu Wang, Hua Zhang, Priyam Jani, Xiaofang Wang, Yongbo Lu, Nan Li, Jing Xiao, Chunlin Qin
FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse. Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney. Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner. To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus...
February 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29297744/tgfb1-is-secreted-through-an-unconventional-pathway-dependent-on-the-autophagic-machinery-and-cytoskeletal-regulators
#19
Julian Nüchel, Sushmita Ghatak, Alexandra V Zuk, Anja Illerhaus, Matthias Mörgelin, Katrin Schönborn, Katrin Blumbach, Sara A Wickström, Thomas Krieg, Gerhard Sengle, Markus Plomann, Beate Eckes
TGFB1 (transforming growth factor beta 1) is a potent cytokine playing a driving role in development, fibrosis and cancer. It is synthesized as prodomain-growth factor complex that requires tethering to LTBP (latent transforming growth factor beta binding protein) for efficient secretion into the extracellular space. Upon release, this large latent complex is sequestered by anchorage to extracellular matrix (ECM) networks, from which the mature growth factor needs to be activated in order to reach its receptors and initiate signaling...
March 11, 2018: Autophagy
https://www.readbyqxmd.com/read/29290941/eucalyptol-ameliorates-snail1-%C3%AE-catenin-dependent-diabetic-disjunction-of-renal-tubular-epithelial-cells-and-tubulointerstitial-fibrosis
#20
Dong Yeon Kim, Min-Kyung Kang, Sin-Hye Park, Eun-Jung Lee, Yun-Ho Kim, Hyeongjoo Oh, Yean-Jung Choi, Young-Hee Kang
Renal tubulointerstitial fibrosis is an important event in the pathogenesis of diabetic nephropathy. Under pathologic conditions, renal tubular epithelial cells undergo transition characterized by loss of cell-cell adhesion and increased cell migration. This study investigated that eucalyptol inhibited tubular epithelial cell disjunction and tubulointerstitial fibrosis stimulated by glucose. Human renal proximal tubular epithelial cells were incubated for up to 72 h in media containing 27.5 mM mannitol as osmotic controls or 33 mM glucose in the presence of 1-20 μM eucalyptol...
December 5, 2017: Oncotarget
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