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Focal adhesion kinase

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https://www.readbyqxmd.com/read/28807942/nuclear-fak-and-runx1-cooperate-to-regulate-igfbp3-cell-cycle-progression-and-tumor-growth
#1
Marta Canel, Adam Byron, Andrew H Sims, Jessy Cartier, Hitesh Patel, Margaret C Frame, Valerie G Brunton, Bryan Serrels, Alan Serrels
Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here we report in a murine model of skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription of insulin-like growth factor binding protein 3 (IGFBP3), and that this regulates SCC cell cycle progression and tumor growth in vivo. Furthermore, we identified a novel molecular complex between FAK and Runx1 in the nucleus of SCC cells and showed that FAK interacted with a number of Runx1 regulatory proteins, including Sin3a and other epigenetic modifiers known to alter Runx1 transcriptional function through post-translational modification...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28783172/p38-delta-mapk-promotes-breast-cancer-progression-and-lung-metastasis-by-enhancing-cell-proliferation-and-cell-detachment
#2
M Wada, D Canals, M Adada, N Coant, M F Salama, K L Helke, J S Arthur, K R Shroyer, K Kitatani, L M Obeid, Y A Hannun
The protein p38 mitogen-activated protein kinase (MAPK) delta isoform (p38δ) is a poorly studied member of the MAPK family. Data analysis from The Cancer Genome Atlas database revealed that p38δ is highly expressed in all types of human breast cancers. Using a human breast cancer tissue array, we confirmed elevation in cancer tissue. The breast cancer mouse model, MMTV-PyMT (PyMT), developed breast tumors with lung metastasis; however, mice deleted in p38δ (PyMT/p38δ(-/-)) exhibited delayed primary tumor formation and highly reduced lung metastatic burden...
August 7, 2017: Oncogene
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
#3
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/28782937/regulation-of-focal-adhesion-kinase-through-a-direct-interaction-with-an-endogenous-inhibitor
#4
Taylor J Zak, Yevgenia E Koshman, Allen M Samarel, Seth L Robia
Focal adhesion kinase (FAK) plays a key role in integrin and growth factor signaling pathways. FAK related non-kinase (FRNK) is an endogenous inhibitor of FAK that shares its primary structure with the C-terminal third of FAK. FAK S910 phosphorylation is known to regulate FAK protein-protein interactions, but the role of the equivalent site on FRNK (S217) is unknown. Here we determined that S217 is highly phosphorylated by ERK in cultured rat aortic smooth muscle cells. Blocking phosphorylation by mutation (S217A) greatly increased FRNK inhibitory potency, resulting in strong inhibition of FAK autophosphorylation at Y397 and induction of smooth muscle cell apoptosis...
August 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/28775097/platelet-derived-growth-factor-receptor-alpha-pdgfr%C3%AE-and-ras-related-c3-botulinum-toxin-substrate-1-rac1-regulate-mechano-responsiveness-of-lung-fibroblasts
#5
Stephen E McGowan, Diann M McCoy
Platelet-derived growth factor (PDGF)-A, which only signals through PDGF-receptor-alpha (PDGFRα) is required for secondary alveolar septal formation. Although PDGFRα distinguishes mesenchymal progenitor cells during the saccular stage, PDGFRα-expressing alveolar cells persist through adulthood. PDGF-A sustains proliferation, limits apoptosis, and maintains alpha-smooth muscle actin (αSMA) containing alveolar cells, which congregate at the alveolar entry ring at postnatal day (P)12. PDGFRα-expressing, αSMA-containing, alveolar cells re-distribute in the elongating septum, suggesting that they migrate to the alveolar entry rings where mechanical tension is higher...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28772425/laser-sintered-magnesium-calcium-silicate-poly-%C3%AE%C2%B5-caprolactone-scaffold-for-bone-tissue-engineering
#6
Kuo-Yang Tsai, Hung-Yang Lin, Yi-Wen Chen, Cheng-Yao Lin, Tuan-Ti Hsu, Chia-Tze Kao
In this study, we manufacture and analyze bioactive magnesium-calcium silicate/poly-ε-caprolactone (Mg-CS/PCL) 3D scaffolds for bone tissue engineering. Mg-CS powder was incorporated into PCL, and we fabricated the 3D scaffolds using laser sintering technology. These scaffolds had high porosity and interconnected-design macropores and structures. As compared to pure PCL scaffolds without an Mg-CS powder, the hydrophilic properties and degradation rate are also improved. For scaffolds with more than 20% Mg-CS content, the specimens become completely covered by a dense bone-like apatite layer after soaking in simulated body fluid for 1 day...
January 13, 2017: Materials
https://www.readbyqxmd.com/read/28765922/electric-field-exposure-promotes-epithelial%C3%A2-mesenchymal-transition-in-human-lens-epithelial-cells-via-integrin-%C3%AE-1%C3%A2-fak-signaling
#7
Jun Liu, Xiao-Long Yan, Xiao-Liang Zheng, Lin Mei, Song Wang, Jing Han, Hong Yan
Electric field (EF) exposure can affect the elongation, migration, orientation, and division of cells. The present study tested the hypothesis that EF may also affect epithelial‑mesenchymal transition (EMT) in lens epithelial cells and that this effect may be an important inducer in the pathological process of posterior capsule opacification (PCO). Human lens epithelial (HLE)‑B3 cells were exposed to an EF. Experiments were performed in the presence or absence of an anti‑integrin β1 blocking antibody or a small molecule inhibitor targeting focal adhesion kinase (FAK)...
July 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28764292/focal-adhesion-kinase-expression-in-ameloblastoma-a-preliminary-observational-study
#8
Snehal Patil, Gargi Sachin Sarode, Sachin C Sarode, Rahul Anand, Shankargouda Patil
INTRODUCTION: Focal Adhesion Kinase (FAK) is a membrane-associated molecule, which plays a major role in tumourigenesis by promoting cell survival, proliferation, migration, and invasion. Hence, FAK is a well known molecule that has been targeted therapeutically for the treatment of various malignancies. Ameloblastoma (AB) is a locally invasive, destructive and recurrent benign odontogenic lesion. Based on these properties, we have hypothesized that odontogenic epithelium of AB could show increased expression of FAK...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28763805/%C3%AE-1-integrin-deletion-from-the-lens-activates-cellular-stress-responses-leading-to-apoptosis-and-fibrosis
#9
Yichen Wang, Anne M Terrell, Brittany A Riggio, Deepti Anand, Salil A Lachke, Melinda K Duncan
Purpose: Previous research showed that the absence of β1-integrin from the mouse lens after embryonic day (E) 13.5 (β1MLR10) leads to the perinatal apoptosis of lens epithelial cells (LECs) resulting in severe microphthalmia. This study focuses on elucidating the molecular connections between β1-integrin deletion and this phenotype. Methods: RNA sequencing was performed to identify differentially regulated genes (DRGs) in β1MLR10 lenses at E15.5. By using bioinformatics analysis and literature searching, Egr1 (early growth response 1) was selected for further study...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28763253/alda-1-protects-against-acrolein-induced-acute-lung-injury-and-endothelial-barrier-dysfunction
#10
Qing Lu, Miles Mundy, Eboni Chambers, Thilo Lange, Julie Newton, Diana Borgas, Hongwei Yao, Gaurav Choudhary, Rajshekhar Basak, Mahogany Oldham, Sharon Rounds
Inhalation of acrolein, a highly reactive aldehyde, causes lung edema. The underlying mechanism is poorly understood and there is no effective treatment. In this study, we demonstrated that acrolein not only dose-dependently induced lung edema, but also promoted lipopolysaccharide (LPS)-induced acute lung injury (ALI). Importantly, acrolein-induced lung injury were prevented and rescued by Alda-1, an activator of mitochondrial aldehyde dehydrogenase (ALDH) 2. Acrolein also dose-dependently increased monolayer permeability, disrupted adherens junctions and focal adhesion complexes, and caused intercellular gap formation in primary cultured lung microvascular endothelial cells (LMVEC); effects that were attenuated by Alda-1 and the antioxidant, N-acetylcysteine, but not by the NADPH inhibitor, apocynin...
August 1, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28759036/deficiency-in-vhr-dusp3-a-suppressor-of-focal-adhesion-kinase-reveals-its-role-in-regulating-cell-adhesion-and-migration
#11
Y-R Chen, H-C Chou, C-H Yang, H-Y Chen, Y-W Liu, T-Y Lin, C-L Yeh, W-T Chao, H-H Tsou, H-C Chuang, T-H Tan
Vaccinia H1-related phosphatase (VHR/DUSP3) is a member of the dual-specificity phosphatase family. Deregulation of VHR is observed in various malignant diseases. We identified focal adhesion kinase (FAK) as a VHR-interacting molecule. Over-expression of VHR decreased tyrosine phosphorylation of FAK and decreasing VHR promoted FAK tyrosine phosphorylation. In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. VHR-knockout mice did not have obvious abnormality; however, VHR-knockout cells showed decreased expression of integrins and FAK but stronger FAK and paxillin phosphorylation upon attachment to fibronectin...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28759022/mir-151a-induces-partial-emt-by-regulating-e-cadherin-in-nsclc-cells
#12
I Daugaard, K J Sanders, A Idica, K Vittayarukskul, M Hamdorf, J D Krog, R Chow, D Jury, L L Hansen, H Hager, P Lamy, C L Choi, D Agalliu, D G Zisoulis, I M Pedersen
miR-151a and its host gene, focal adhesion kinase, FAK, are located in a region of chromosome 8q that is frequently amplified in solid tumors, including lung cancer. Lung cancer is the leading cause of cancer deaths worldwide and metastasis remains the major challenge in battling lung cancer mortality. Here, we demonstrate that miR-151a is overexpressed in non-small cell lung cancer (NSCLC) patient specimens, as compared to healthy lung. In addition, miR-151a overexpression promotes proliferation, epithelial-to-mesenchymal transition (EMT) and induces tumor cell migration and invasion of NSCLC cells...
July 31, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28757207/focal-adhesion-and-igf1r-dependent-survival-and-migratory-pathways-mediate-tumor-resistance-to-mtorc1-2-inhibition
#13
Sang-Oh Yoon, Sejeong Shin, Florian A Karreth, Gwen R Buel, Mark P Jedrychowski, David R Plas, Shoukat Dedhar, Steven P Gygi, Philippe P Roux, Noah Dephoure, John Blenis
Aberrant signaling by the mammalian target of rapamycin (mTOR) contributes to the devastating features of cancer cells. Thus, mTOR is a critical therapeutic target and catalytic inhibitors are being investigated as anti-cancer drugs. Although mTOR inhibitors initially block cell proliferation, cell viability and migration in some cancer cells are quickly restored. Despite sustained inhibition of mTORC1/2 signaling, Akt, a kinase regulating cell survival and migration, regains phosphorylation at its regulatory sites...
August 3, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28755662/substrate-stiffness-governs-the-initiation-of-b-cell-activation-by-the-concerted-signaling-of-pkc%C3%AE-and-focal-adhesion-kinase
#14
Samina Shaheen, Zhengpeng Wan, Zongyu Li, Alicia Chau, Xinxin Li, Shaosen Zhang, Yang Liu, Junyang Yi, Yingyue Zeng, Jing Wang, Xiangjun Chen, Liling Xu, Wei Chen, Fei Wang, Yun Lu, Wenjie Zheng, Yan Shi, Xiaolin Sun, Zhanguo Li, Chunyang Xiong, Wanli Liu
The mechanosensing ability of lymphocytes regulates their activation in response to antigen stimulation, but the underlying mechanism remains unexplored. Here, we report that B cell mechanosensing-governed activation requires BCR signaling molecules. PMA-induced activation of PKCβ can bypass the Btk and PLC-γ2 signaling molecules that are usually required for B cells to discriminate substrate stiffness. Instead, PKCβ-dependent activation of FAK is required, leading to FAK-mediated potentiation of B cell spreading and adhesion responses...
July 31, 2017: ELife
https://www.readbyqxmd.com/read/28754835/in-vivo-functional-selection-identifies-cardiotrophin-1-as-a-cardiac-engraftment-factor-for-mesenchymal-stromal-cells
#15
Francesca Bortolotti, Giulia Ruozi, Antonella Falcione, Sara Doimo, Matteo Dal Ferro, Pierluigi Lesizza, Lorena Zentilin, Lawrence Banks, Serena Zacchigna, Mauro Giacca
Background -Transplantation of cells into the infarcted heart has significant potential to improve myocardial recovery; however, low efficacy of cell engraftment still limits therapeutic benefit. Here we describe a method for the unbiased, in vivo selection of cytokines that improve mesenchymal stromal cell (MSC) engraftment into the heart in both normal conditions and after myocardial infarction. Methods -An arrayed library of 80 secreted factors, including most of the currently known interleukins and chemokines, were individually cloned into adeno-associated viral (AAV) vectors...
July 28, 2017: Circulation
https://www.readbyqxmd.com/read/28752652/y-27632-simplifies-the-isolation-procedure-of-human-primary-epidermal-cells-by-selectively-blocking-focal-adhesion-of-dermal-cells
#16
Jie Wen, Tingjian Zu, Qian Zhou, Xue Leng, Xunwei Wu
Primary skin epidermal cells isolation and in vitro expansion culture has been widely used for laboratory research and clinical applications. The conventional methods involving sequential enzymatic digestion of adult tissues have given low cell recovery rate and reduced cell viability. We report here an advanced method for human primary epidermal progenitor cells isolation from skin tissues including the Rho kinase inhibitor Y-27632. Compared to traditional protocols, the current protocol is simple, easy and faster; moreover, it gives a greater yield of integrin-expressing epithelial stem cells...
July 27, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28751568/mtor-mechanistic-target-of-rapamycin-inhibition-decreases-mechanosignaling-collagen-accumulation-and-stiffening-of-the-thoracic-aorta-in-elastin-deficient-mice
#17
Yang Jiao, Guangxin Li, Qingle Li, Rahmat Ali, Lingfeng Qin, Wei Li, Yibing Qyang, Daniel M Greif, Arnar Geirsson, Jay D Humphrey, George Tellides
OBJECTIVE: Elastin deficiency because of heterozygous loss of an ELN allele in Williams syndrome causes obstructive aortopathy characterized by medial thickening and fibrosis and consequent aortic stiffening. Previous work in Eln-null mice with a severe arterial phenotype showed that inhibition of mTOR (mechanistic target of rapamycin), a key regulator of cell growth, lessened the aortic obstruction but did not prevent early postnatal death. We investigated the effects of mTOR inhibition in Eln-null mice partially rescued by human ELN that manifest a less severe arterial phenotype and survive long term...
July 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28744198/galectin-3-negatively-regulates-hippocampus-dependent-memory-formation-through-inhibition-of-integrin-signaling-and-galectin-3-phosphorylation
#18
Yan-Chu Chen, Yun-Li Ma, Cheng-Hsiung Lin, Sin-Jhong Cheng, Wei-Lun Hsu, Eminy H-Y Lee
Galectin-3, a member of the galectin protein family, has been found to regulate cell proliferation, inhibit apoptosis and promote inflammatory responses. Galectin-3 is also expressed in the adult rat hippocampus, but its role in learning and memory function is not known. Here, we found that contextual fear-conditioning training, spatial training or injection of NMDA into the rat CA1 area each dramatically decreased the level of endogenous galectin-3 expression. Overexpression of galectin-3 impaired fear memory, whereas galectin-3 knockout (KO) enhanced fear retention, spatial memory and hippocampal long-term potentiation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28743863/transcriptome-analysis-of-canine-cutaneous-melanoma-and-melanocytoma-reveals-a-modulation-of-genes-regulating-extracellular-matrix-metabolism-and-cell-cycle
#19
Chiara Brachelente, Katia Cappelli, Stefano Capomaccio, Ilaria Porcellato, Serenella Silvestri, Laura Bongiovanni, Raffaella De Maria, Andrea Verini Supplizi, Luca Mechelli, Monica Sforna
Interactions between tumor cells and tumor microenvironment are considered critical in carcinogenesis, tumor invasion and metastasis. To examine transcriptome changes and to explore the relationship with tumor microenvironment in canine cutaneous melanocytoma and melanoma, we extracted RNA from formalin-fixed, paraffin-embedded (FFPE) specimens and analyzed them by means of RNA-seq for transcriptional analysis. Melanocytoma and melanoma samples were compared to detect differential gene expressions and significant enriched pathways were explored to reveal functional relations between differentially expressed genes...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743627/characterization-of-a-novel-non-receptor-tyrosine-kinase-src-from-litopenaeus-vannamei-and-its-response-to-white-spot-syndrome-virus-infection
#20
Defu Yao, Lingwei Ruan, Jingxiang Xu, Hong Shi, Xun Xu
Src family kinases (SFKs), a class of non-receptor tyrosine kinases, mediate a wide aspect of cellular signaling pathways that regulate cell proliferation, differentiation, motility and survival. In this study, we identified and characterized for the first time a novel SFK homologue from Litopenaeus vannamei (designated as LvSrc). Sequence analysis showed that LvSrc had a high homology with the identified SFKs, especially those from invertebrates. LvSrc contained the conserved SH3, SH2 and tyrosine kinase domains, as well as the potential phosphorylation and lipid modification sites...
July 23, 2017: Fish & Shellfish Immunology
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