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Focal adhesion kinase

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https://www.readbyqxmd.com/read/28316141/dasatinib-inhibits-actin-fiber-reorganization-and-promotes-endothelial-cell-permeability-through-rhoa-rock-pathway
#1
Swapan K Dasgupta, Anhquyen Le, K Vinod Vijayan, Perumal Thiagarajan
Treatment with dasatinib, a tyrosine kinase inhibitor, is associated with edema, pleural effusion, and pulmonary edema. We investigated the effect of dasatinib on the barrier function of human microvascular endothelial cells-1 (HMEC-1) in vitro and in vivo. The permeability of HMEC-1 to fluorescein isothiocyante (FITC)-dextran increased in Transwell chambers within 5 min following the addition of therapeutic concentrations of dasatinib. The change in permeability was associated with increased activation of RhoA GTPase and its effector Rho-associated coiled-coil kinase 1(ROCK1)...
March 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28314297/expression-and-clinical-significance-of-concomitant-fak-src-and-p-paxillin-in-mobile-tongue-squamous-cell-carcinoma
#2
Stamatios Theocharis, Ioly Kotta-Loizou, Constantinos Giaginis, Paraskevi Alexandrou, Eugene Danas, Gerasimos Tsourouflis, Nikolaos Tsoukalas, Robert H A Coutts, Jason Tasoulas, Jerzy Klijanienko
BACKGROUND/AIM: The focal adhesion kinase (FAK)/SRC phosphorylation cascade and its downstream target paxillin have been implicated in malignant transformation, tumor growth and progression, together with metastasis. The present study aimed to evaluate the clinical significance of concomitant FAK/SRC and p-paxillin expression in mobile tongue squamous cell carcinoma (SCC). MATERIALS AND METHODS: FAK, SRC and phospho-paxillin expression in 48 mobile tongue SCC tissue samples was assessed immunohistochemically and analyzed with respect to clinicopathological characteristics and patient survival...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28306722/distinct-erbb2-receptor-populations-differentially-interact-with-beta1-integrin-in-breast-cancer-cell-models
#3
Andrés Martín Toscani, Rocío G Sampayo, Federico Martín Barabas, Federico Fuentes, Marina Simian, Federico Coluccio Leskow
ErbB2 is a member of the ErbB family of tyrosine kinase receptors that plays a major role in breast cancer progression. Located at the plasma membrane, ErbB2 forms large clusters in spite of the presence of growth factors. Beta1 integrin, membrane receptor of extracellular matrix proteins, regulates adhesion, migration and invasiveness of breast cancer cells. Physical interaction between beta1 integrin and ErbB2 has been suggested although published data are contradictory. The aim of the present work was to study the interaction between ErbB2 and beta1 integrin in different scenarios of expression and activation...
2017: PloS One
https://www.readbyqxmd.com/read/28306605/hyperalgesic-priming-type-ii-induced-by-repeated-opioid-exposure-maintenance-mechanisms
#4
Dioneia Araldi, Luiz F Ferrari, Jon D Levine
We previously developed a model of opioid-induced neuroplasticity in the peripheral terminal of the nociceptor that could contribute to opioid-induced hyperalgesia, type II hyperalgesic priming. Repeated administration of mu-opioid receptor (MOR) agonists, such as DAMGO, at the peripheral terminal of the nociceptor, induces long-lasting plasticity expressed, prototypically as opioid-induced hyperalgesia and prolongation of prostaglandin-E2-induced hyperalgesia. In this study, we evaluated the mechanisms involved in the maintenance of type II priming...
March 14, 2017: Pain
https://www.readbyqxmd.com/read/28302906/distinct-focal-adhesion-protein-modules-control-different-aspects-of-mechanotransduction
#5
Ben Stutchbury, Paul Atherton, Ricky Tsang, De-Yao Wang, Christoph Ballestrem
Focal adhesions (FAs) are macromolecular complexes that regulate cell adhesion and mechanotransduction. Using fluorescence recovery after photobleaching (FRAP) and fluorescence loss after photoactivation (FLAP), we found that the mobility of core FA proteins correlates with protein function. Structural proteins such as tensin, talin and vinculin are significantly less mobile in FAs than signaling proteins such as FAK and paxillin. The mobilities of the structural proteins are directly influenced by substrate stiffness, suggesting they are involved in sensing the rigidity of the extracellular environment...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28293103/protective-influence-of-hyaluronic-acid-on-focal-adhesion-kinase-activity-in-human-skin-fibroblasts-exposed-to-ethanol
#6
Magdalena Donejko, Edyta Rysiak, Elżbieta Galicka, Robert Terlikowski, Edyta Katarzyna Głażewska, Andrzej Przylipiak
AIM: The aim of this study was to evaluate the effect of ethanol and hyaluronic acid (HA) on cell survival and apoptosis in cultured human skin fibroblasts. Regarding the mechanism of ethanol action on human skin fibroblasts, we investigated cell viability and apoptosis, expression of focal adhesion kinase (FAK), and the influence of HA on those processes. MATERIALS AND METHODS: Studies were conducted in confluent human skin fibroblast cultures that were treated with 25 mM, 50 mM, and 100 mM ethanol or with ethanol and 500 µg/mL HA...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28290610/kindlin-1-contributes-to-egf-induced-re-epithelialization-in-skin-wound-healing
#7
Congcong Shen, Linlin Sun, Ningwen Zhu, Fazhi Qi
The commercial use of epidermal growth factor (EGF) is extensive and has been shown to be effective for skin wound healing in clinical practice. There is evidence to indicate that the topical administration of EGF significantly accelerates re-epithelialization by promoting keratinocyte mitogenesis and migration following acute injury; however, the mechanisms involved remain to be elucidated. Thus, in this study, we focused on Kindlin-1, a four-point-one, ezrin, radixin, moesin (FERM)-domain-containing adaptor protein, and report its contribution to EGF-induced re-epithelialization in skin wound healing...
March 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28289710/targeting-adhesion-signaling-in-kras-lkb1-mutant-lung-adenocarcinoma
#8
Melissa Gilbert-Ross, Jessica Konen, Junghui Koo, John Shupe, Brian S Robinson, Walter Guy Wiles, Chunzi Huang, W David Martin, Madhusmita Behera, Geoffrey H Smith, Charles E Hill, Michael R Rossi, Gabriel L Sica, Manali Rupji, Zhengjia Chen, Jeanne Kowalski, Andrea L Kasinski, Suresh S Ramalingam, Haian Fu, Fadlo R Khuri, Wei Zhou, Adam I Marcus
Loss of LKB1 activity is prevalent in KRAS mutant lung adenocarcinoma and promotes aggressive and treatment-resistant tumors. Previous studies have shown that LKB1 is a negative regulator of the focal adhesion kinase (FAK), but in vivo studies testing the efficacy of FAK inhibition in LKB1 mutant cancers are lacking. Here, we took a pharmacologic approach to show that FAK inhibition is an effective early-treatment strategy for this high-risk molecular subtype. We established a lenti-Cre-induced Kras and Lkb1 mutant genetically engineered mouse model (KLLenti) that develops 100% lung adenocarcinoma and showed that high spatiotemporal FAK activation occurs in collective invasive cells that are surrounded by high levels of collagen...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28288918/increased-carbon-dioxide-levels-stimulate-neutrophils-to-produce-microparticles-and-activate-the-nucleotide-binding-domain-like-receptor-3-inflammasome
#9
Stephen R Thom, Veena M Bhopale, JingPing Hu, Ming Yang
We hypothesized that elevations of carbon dioxide (CO2) commonly found in modern buildings will stimulate leukocytes to produce microparticles (MPs) and activate the nucleotide-binding domain-like receptor 3 (NLRP3) inflammasome due to mitochondrial oxidative stress. Human and murine neutrophils generate MPs with high interleukin-1β (IL-1β) content when incubated ex vivo in buffer equilibrated with 0.1 to 0.4% additional CO2. Enhanced MPs production requires mitochondrial reactive oxygen species production, which is mediated by activities of pyruvate carboxylase and phosphoenolpyruvate carboxykinase...
March 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28287465/serine-threonine-kinase-3-phosphoinositide-dependent-protein-kinase-1-pdk1-as-a-key-regulator-of-cell-migration-and-cancer-dissemination
#10
REVIEW
Laura Di Blasio, Paolo A Gagliardi, Alberto Puliafito, Luca Primo
Dissecting the cellular signaling that governs the motility of eukaryotic cells is one of the fundamental tasks of modern cell biology, not only because of the large number of physiological processes in which cell migration is crucial, but even more so because of the pathological ones, in particular tumor invasion and metastasis. Cell migration requires the coordination of at least four major processes: polarization of intracellular signaling, regulation of the actin cytoskeleton and membrane extension, focal adhesion and integrin signaling and contractile forces generation and rear retraction...
March 11, 2017: Cancers
https://www.readbyqxmd.com/read/28287129/akt1-and-akt2-isoforms-play-distinct-roles-during-breast-cancer-progression-through-the-regulation-of-specific-downstream-proteins
#11
Marina Riggio, María C Perrone, María L Polo, María J Rodriguez, María May, Martín Abba, Claudia Lanari, Virginia Novaro
The purpose of this study was to elucidate the mechanisms associated with the specific effects of AKT1 and AKT2 isoforms in breast cancer progression. We modulated the abundance of specific AKT isoforms in IBH-6 and T47D human breast cancer cell lines and showed that AKT1 promoted cell proliferation, through S6 and cyclin D1 upregulation, but it inhibited cell migration and invasion through β1-integrin and focal adhesion kinase (FAK) downregulation. In contrast, AKT2 promoted cell migration and invasion through F-actin and vimentin induction...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286248/cell-migration-in-schizophrenia-schizophrenia-patient-derived-cells-do-not-regulate-motility-in-response-to-extracellular-matrix
#12
Jing Yang Tee, Ratneswary Sutharsan, Yongjun Fan, Alan Mackay-Sim
Schizophrenia is a highly heritable psychiatric disorder linked to a large number of risk genes. The function of these genes in disease etiology is not fully understood but pathway analyses of genomic data suggest developmental dysregulation of cellular processes such as neuronal migration and axon guidance. Previous studies of patient-derived olfactory cells show them to be more motile than control-derived cells when grown on a fibronectin substrate, motility that is dependent on focal adhesion kinase signaling...
March 9, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28286026/clonorchis-sinensis-excretory-secretory-products-promote-the-migration-and-invasion-of-cholangiocarcinoma-cells-by-activating-the-integrin-%C3%AE-4-fak-src-signaling-pathway
#13
Jhang Ho Pak, Qudsia Bashir, In Ki Kim, Sung-Jong Hong, Sejung Maeng, Young Yil Bahk, Tong-Soo Kim
Cholangiocarcinoma (CCA) is a slow-growing but highly metastatic cancer. Its metastatic potential largely explains its high mortality rate. A recognized risk factor for CCA development is infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis. We previously reported that the excretory-secretory products (ESPs) of C. sinensis promoted the three-dimensional aggregation and invasion of CCA cells. In the present study, a quantitative real-time PCR array of extracellular matrix (ECM) and adhesion molecules was used to examine the regulatory mechanism of ESP-mediated CCA cell migration and invasion...
March 7, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28284838/prl-3-ptp4a3-phosphatase-regulates-integrin-%C3%AE-1-in-adhesion-structures-during-migration-of-human-ocular-melanoma-cells
#14
Malika Foy, Océane Anézo, Simon Saule, Nathalie Planque
In a previous transcriptomic analysis of 63 ocular melanomas of the uvea, we found that expression of the PRL-3/PTP4A3 gene, encoding a phosphatase that is anchored to the plasma membrane, was associated with the risk of metastasis, and a poor prognosis. We also showed that PRL-3 overexpression in OCM-1 ocular melanoma cells significantly increased cell migration in vitro and invasiveness in vivo, suggesting a direct role for PRL-3 in the metastatic spreading of uveal melanoma. Here, we aimed to identify PRL-3 substrates at the plasma membrane involved in adhesion to the extracellular matrix...
March 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28284808/synthesis-of-novel-1-2-4-triazine-scaffold-as-fak-inhibitors-with-antitumor-activity
#15
Pascal Dao, Daniel Lietha, Mélanie Etheve-Quelquejeu, Christiane Garbay, Huixiong Chen
A series of 1,3,5-triazinic inhibitors of focal adhesion kinase (FAK) has recently been shown to exert antiangiogenic activity against HUVEC cells and anticancer efficacy against several cancer cell lines. In this report, we designed and synthesized a series of new compounds containing a 1,2,4-triazine core as novel scaffold for FAK inhibitors. These compounds displayed 10(-7)M IC50 values, and the best one showed IC50 value of 0.23μM against FAK enzymatic activity. Among them, several inhibitors potently inhibited the proliferation of glioblastoma (U-87MG) and colon (HCT-116) cancer cell lines...
February 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28283477/lung-epithelial-cell-focal-adhesion-kinase-signaling-inhibits-lung-injury-and-fibrosis
#16
Amanda K Wheaton, Manisha Agarwal, Shijing Jia, Kevin K Kim
Progressive pulmonary fibrosis is a devastating consequence of many acute and chronic insults to the lung. Lung injury leads to alveolar epithelial cell (AEC) death, destruction of the basement membrane and activation of TGFβ. There is subsequent resolution of the injury and a coordinated and concurrent initiation of fibrosis. Both of these processes may involve activation of similar intracellular signaling pathways regulated in part by dynamic changes to the extracellular matrix. Matrix signaling can augment the pro-fibrotic fibroblast response to TGFβ...
March 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28276928/plectin-deficiency-in-liver-cancer-cells-promotes-cell-migration-and-sensitivity-to-sorafenib-treatment
#17
Chiung-Chi Cheng, Wei-Ting Chao, Chen-Chun Liao, Yu-Hui Tseng, Yen-Chang Clark Lai, Yih-Shyong Lai, Yung-Hsiang Hsu, Yi-Hsiang Liu
Plectin involved in activation of kinases in cell signaling pathway and plays important role in cell morphology and migration. Plectin knockdown promotes cell migration by activating focal adhesion kinase and Rac1-GTPase activity in liver cells. Sorafenib is a multi-targeting tyrosine kinase inhibitor that improves patient survival on hepatocellular carcinoma. The aim of this study is to investigate the correlation between the expression of plectin and cell migration as well as the sensitivity of hepatoma cell lines exposing to sorafenib...
February 17, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28274158/heat-shock-protein-antagonists-in-early-stage-clinical-trials-for-nsclc
#18
Lizza E L Hendriks, Anne-Marie C Dingemans
Cancer cells have a higher need of chaperones than normal cells to prevent the toxic effects of intracellular protein misfolding and aggregation. Heat shock proteins (Hsps) belong to these chaperones; they are classified into families according to molecular size. Hsps are upregulated in many cancers and inhibition can inhibit tumor growth by destabilizing proteins necessary for tumor survival. In non-small cell lung cancer (NSCLC), there are three different Hsp antagonist classes that are in (early) clinical trials: Hsp90, Hsp70 and Hsp27 inhibitors...
March 8, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28273809/proteome-analysis-of-human-follicular-thyroid-cancer-cells-exposed-to-the-random-positioning-machine
#19
Johann Bauer, Sascha Kopp, Elisabeth Maria Schlagberger, Jirka Grosse, Jayashree Sahana, Stefan Riwaldt, Markus Wehland, Ronald Luetzenberg, Manfred Infanger, Daniela Grimm
Several years ago, we detected the formation of multicellular spheroids in experiments with human thyroid cancer cells cultured on the Random Positioning Machine (RPM), a ground-based model to simulate microgravity by continuously changing the orientation of samples. Since then, we have studied cellular mechanisms triggering the cells to leave a monolayer and aggregate to spheroids. Our work focused on spheroid-related changes in gene expression patterns, in protein concentrations, and in factors secreted to the culture supernatant during the period when growth is altered...
March 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28270436/focal-adhesion-kinase-as-a-potential-target-in-aml-and-mds
#20
Bing Z Carter, Po Yee Mak, Xiangmeng Wang, Hui Yang, Guillermo Garcia-Manero, Duncan Mak, Hong Mu, Vivian Ruvolo, Yihua Qiu, Kevin Coombes, Nianxiang Zhang, Brittany Ragon, David T Weaver, Jonathan A Pachter, Steven Kornblau, Michael Andreeff
Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics (P = 2 x 10-4) and relapse (P = 0...
March 7, 2017: Molecular Cancer Therapeutics
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