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Integrin linked kinase

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https://www.readbyqxmd.com/read/29038237/the-gain-of-function-integrin-%C3%AE-3-pro33-variant-alters-the-serotonin-system-in-the-mouse-brain
#1
Michael R Dohn, Christopher G Kooker, Lisa Bastarache, Tammy Jessen, Capria Rinaldi, Seth Varney, Matthew D Mazalouskas, Hope Pan, Kendra H Oliver, Digna R Velez Edwards, James S Sutcliffe, Joshua C Denny, Ana M D Carneiro
Engagement of integrins by the extracellular matrix initiates signaling cascades that drive a variety of cellular functions, including neuronal migration and axonal pathfinding in the brain. Multiple lines of evidence link the ITGB3 gene encoding the integrin β3 subunit with the serotonin (5-HT) system, likely via its modulation of the 5-HT transporter (SERT). The ITGB3 coding polymorphism Leu33Pro (rs5918, Pl(A2)) produces hyperactive αvβ3 receptors that influence whole blood 5-HT levels and may influence risk for autism spectrum disorder (ASD)...
October 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29030401/a-comparison-of-whole-genome-sequencing-to-multigene-panel-testing-in-hypertrophic-cardiomyopathy-patients
#2
Allison L Cirino, Neal K Lakdawala, Barbara McDonough, Lauren Conner, Dale Adler, Mark Weinfeld, Patrick O'Gara, Heidi L Rehm, Kalotina Machini, Matthew Lebo, Carrie Blout, Robert C Green, Calum A MacRae, Christine E Seidman, Carolyn Y Ho
BACKGROUND: As DNA sequencing costs decline, genetic testing options have expanded. Whole exome sequencing and whole genome sequencing (WGS) are entering clinical use, posing questions about their incremental value compared with disease-specific multigene panels that have been the cornerstone of genetic testing. METHODS AND RESULTS: Forty-one patients with hypertrophic cardiomyopathy who had undergone targeted hypertrophic cardiomyopathy genetic testing (either multigene panel or familial variant test) were recruited into the MedSeq Project, a clinical trial of WGS...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29020611/tubulin-dependent-secretion-of-s100a6-and-cellular-signaling-pathways-activated-by-s100a6-integrin-%C3%AE-1-interaction
#3
Ewelina Jurewicz, Elżbieta Wyroba, Anna Filipek
S100A6 is a calcium binding protein expressed mainly in fibroblasts and epithelial cells. Interestingly, S100A6 is also present in extracellular fluids. Recently we have shown that S100A6 is secreted by WJMS cells and binds to integrin β1 (Jurewicz et al., 2014). In this work we describe for the first time the mechanism of S100A6 secretion and signaling pathways activated by the S100A6-integrin β1 complex. We show that colchicine suppressed the release of S100A6 into the cell medium, which indicates that the protein might be secreted via a tubulin-dependent pathway...
October 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29017029/fgf10-hippo-epithelial-mesenchymal-crosstalk-maintains-and-recruits-lung-basal-stem-cells
#4
Thomas Volckaert, Tingting Yuan, Cho-Ming Chao, Harold Bell, Alina Sitaula, Luisa Szimmtenings, Elie El Agha, Diptiman Chanda, Susan Majka, Saverio Bellusci, Victor J Thannickal, Reinhard Fässler, Stijn P De Langhe
The lung harbors its basal stem/progenitor cells (BSCs) in the protected environment of the cartilaginous airways. After major lung injuries, BSCs are activated and recruited to sites of injury. Here, we show that during homeostasis, BSCs in cartilaginous airways maintain their stem cell state by downregulating the Hippo pathway (resulting in increased nuclear Yap), which generates a localized Fgf10-expressing stromal niche; in contrast, differentiated epithelial cells in non-cartilaginous airways maintain quiescence by activating the Hippo pathway and inhibiting Fgf10 expression in airway smooth muscle cells (ASMCs)...
October 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28977901/overexpression-of-stathmin-plays-a-pivotal-role-in-the-metastasis-of-esophageal-squamous-cell-carcinoma
#5
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...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28973887/cross-activating-c-met-%C3%AE-1-integrin-complex-drives-metastasis-and-invasive-resistance-in-cancer
#6
Arman Jahangiri, Alan Nguyen, Ankush Chandra, Maxim K Sidorov, Garima Yagnik, Jonathan Rick, Sung Won Han, William Chen, Patrick M Flanigan, Dina Schneidman-Duhovny, Smita Mascharak, Michael De Lay, Brandon Imber, Catherine C Park, Kunio Matsumoto, Kan Lu, Gabriele Bergers, Andrej Sali, William A Weiss, Manish K Aghi
The molecular underpinnings of invasion, a hallmark of cancer, have been defined in terms of individual mediators but crucial interactions between these mediators remain undefined. In xenograft models and patient specimens, we identified a c-Met/β1 integrin complex that formed during significant invasive oncologic processes: breast cancer metastases and glioblastoma invasive resistance to antiangiogenic VEGF neutralizing antibody, bevacizumab. Inducing c-Met/β1 complex formation through an engineered inducible heterodimerization system promoted features crucial to overcoming stressors during metastases or antiangiogenic therapy: migration in the primary site, survival under hypoxia, and extravasation out of circulation...
September 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28944870/effect-of-integrin%C3%A2-linked-kinase-gene-silencing-on-microrna-expression-in-ovarian-cancer
#7
Dandan Yuan, Yilei Zhao, Yang Wang, Jianhua Che, Wenhua Tan, Yuxia Jin, Fei Wang, Peiliang Li, Shuyan Fu, Qian Liu, Wenliang Zhu
Integrin‑linked kinase (ILK) is overexpressed in ovarian cancer (OC), and ILK gene silencing results in apoptosis in OC cells. In the present study, the mechanism by which ILK induces apoptosis was explored from the perspective of microRNA (miRNA) expression. Alterations in the global miRNA expression profile were detected using a miRNA microarray after OC cells were transduced with an ILK small hairpin RNA lentivirus. ILK silencing led to a significant upregulation of 14 miRNAs by at least 1.5‑fold. These findings were validated by reverse transcription‑quantitative polymerase chain reaction...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28893556/the-ilk-mmp9-mrtf-axis-is-crucial-for-endmt-differentiation-of-endothelial-cells-in-a-tumor-microenvironment
#8
Wojciech M Ciszewski, Katarzyna Sobierajska, Marta E Wawro, Wanda Klopocka, Natasza Chefczyńska, Angelika Muzyczuk, Kamil Siekacz, Agata Wujkowska, Jolanta Niewiarowska
Increasing evidence indicates that the tumor microenvironment is a critical factor supporting cancer progression, chemoresistance and metastasis. Recently, cancer-associated fibroblasts (CAFs) have been recognized as a crucial tumor stromal component promoting cancer growth and invasiveness via modulation of the extracellular matrix (ECM) structure, tumor metabolism and immune reprogramming. One of the main sources of CAFs are endothelial cells undergoing the endothelial-mesenchymal transition (EndMT). EndMT is mainly promoted by the Transforming Growth Factor-β (TGF-β) family secreted by tumor cells, though the role of particular members in EndMT regulation remains poorly understood...
September 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28877984/%C3%AE-5%C3%AE-1-integrinpromotes-tension-dependent-mammary-epithelial-cell-invasion-by-engaging-the-fibronectin-synergy-site
#9
Y A Miroshnikova, G I Rozenberg, L Cassereau, M Pickup, J K Mouw, G Ou, K L Templeman, I Elloumi-Hannachi, K Gooch, A L Sarang-Sieminski, A J García, V M Weaver
Tumors are fibrotic and characterized by abundant, remodeled and cross-linked collagen that stiffens the extracellular matrix stroma. The stiffened collagenous stroma fosters malignant transformation of the tissue by increasing tumor cell tension to promote focal adhesion formation and potentiate growth factor receptor signaling through ERK and PI3 kinase. Importantly, collagen cross-linking requires fibronectin. Fibrotic tumors contain abundant fibronectin and tumor cells frequently up regulate the fibronectin receptor α5β1 integrin...
September 6, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28876503/functional-links-between-disabled-2-ser723-phosphorylation-and-thrombin-signaling-in-human-platelets
#10
H-J Tsai, K-Y Chien, H-R Liao, M-S Shih, Y-C Lin, Y-W Chang, J-C Cheng, C-P Tseng
Essentials Disabled-2 (Dab2) phosphorylation status in thrombin signaling of human platelet was investigated. Ser723 was the major Dab2 phosphorylation site in human platelets stimulated by thrombin. Dab2 S723 phosphorylation (pS723) caused the dissociation of Dab2-CIN85 protein complex. Dab2-pS723 regulated ADP release and integrin αIIbβ3 activation in thrombin-treated platelets. SUMMARY: Background Disabled-2 (Dab2) is a platelet protein that is functionally involved in thrombin signaling in mice...
September 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28867754/sushi-repeat-containing-protein-x-linked-2-promotes-angiogenesis-through-the-urokinase-type-plasminogen-activator-receptor-dependent-integrin-%C3%AE-v%C3%AE-3-focal-adhesion-kinase-pathways
#11
Kuiliang Liu, Jianghao Fan, Jing Wu
Sushi repeat-containing protein X-linked 2 (SRPX2) is a newly identified chondroitin sulfate proteoglycan that is markedly elevated in multiple solid tumors. It is also suggested that SRPX2 is associated with angiogenesis. A conditioned medium of SRPX2 overexpressing colorectal cancer (CRC) cells and SRPX2 recombinant protein was used to evaluate the effect of secretory SRPX2 on the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) and the involved molecular mechanisms. It was revealed that the activity of SRPX2 is dependent on the urokinase-type plasminogen activator receptor and cooperation of the integrin αvβ3 co-receptor...
2017: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/28864764/optogenetic-interrogation-of-integrin-%C3%AE-v%C3%AE-3-function-in-endothelial-cells
#12
Zhongji Liao, Ana Kasirer-Friede, Sanford J Shattil
αVβ3 is reported to promote angiogenesis in some model systems but not in others. Here we used optogenetics to study effects of αVβ3 interaction with the intracellular adapter, kindlin-2, on endothelial cell functions potentially relevant to angiogenesis. Since interaction of kindlin-2 with αVβ3 requires the C-terminal three residues of the β3 cytoplasmic tail (Arg-Gly-Thr; RGT), optogenetic probes LOVpep and ePDZ1 were fused to β3ΔRGT-GFP and mCherry-kindlin2, respectively, and expressed in β3-null microvascular endothelial cells...
September 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28853308/insulin-suppresses-mpp-induced-neurotoxicity-by-targeting-integrins-and-syndecans-in-c6-astrocytes
#13
Mahesh Ramalingam, Mi Hyun Cheng, Sung-Jin Kim
Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly. In central nervous system, astrocytes regulates neuronal function via the modulation of synaptic transmission and plasticity, secretion of growth factors, uptake of neurotransmitters and regulation of extracellular ion concentrations and metabolic support of neurons. Therefore, C6 astroglial cells have been used to study the in vitro PD model induced by 1-methyl-4-phenyl pyridinium (MPP(+)). In this study, pre-treatment of insulin inhibited MPP(+)-induced cell membrane damages on LDH and NO releases, which also inhibited the iNOS and Cox-2 levels...
August 30, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28852375/schwann-cell-development-maturation-and-regeneration-a-focus-on-classic-and-emerging-intracellular-signaling-pathways
#14
REVIEW
Luca Franco Castelnovo, Veronica Bonalume, Simona Melfi, Marinella Ballabio, Deborah Colleoni, Valerio Magnaghi
The development, maturation and regeneration of Schwann cells (SCs), the main glial cells of the peripheral nervous system, require the coordinate and complementary interaction among several factors, signals and intracellular pathways. These regulatory molecules consist of integrins, neuregulins, growth factors, hormones, neurotransmitters, as well as entire intracellular pathways including protein-kinase A, C, Akt, Erk/MAPK, Hippo, mTOR, etc. For instance, Hippo pathway is overall involved in proliferation, apoptosis, regeneration and organ size control, being crucial in cancer proliferation process...
July 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28846213/proteome-dynamics-in-biobanked-horse-peripheral-blood-derived-lymphocytes-pbl-with-induced-autoimmune-uveitis
#15
Stefanie M Hauck, Marlen F Lepper, Michael Hertl, Walter Sekundo, Cornelia A Deeg
Equine recurrent uveitis (ERU) is the only spontaneous model for recurrent autoimmune uveitis in humans, where T cells target retinal proteins. Differences between normal and autoaggressive lymphocytes were identified in this study by analyzing peripheral blood derived lymphocytes (PBL) proteomes from the same case with IRBP-induced uveitis sampled before (day 0), during (day 15) and after uveitic attack (day 23). Relative protein abundances of PBL were investigated in a quantitative, label-free differential proteome analysis in cells that were kept frozen for 14 years since the initial experiment...
August 28, 2017: Proteomics
https://www.readbyqxmd.com/read/28794235/integrin-linked-kinase-expression-in-myeloid-cells-promotes-inflammatory-signaling-during-experimental-colitis
#16
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
#17
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...
October 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
#18
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
#19
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
#20
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
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