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Focal adhesion kinase

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https://www.readbyqxmd.com/read/28230794/structural-determinant-and-its-underlying-molecular-mechanism-of-stpc2-related-to-anti-angiogenic-activity
#1
Min Hu, Ning Cui, Zhixiang Bo, Feixiang Xiang
In this study, we aimed to use different strategies to further uncover the anti-angiogenic molecular mechanism of a fucoidan-like polysaccharide STPC2, isolated from brown alga Sargassum thunbergii. A desulfated derivative, STPC2-DeS, was successfully prepared and identified. The native polysaccharide and desulfated product were subjected to evaluate their anti-angiogenic effects. In the tube formation assay, STPC2 showed dose-dependent inhibition. In addition, STPC2 could distinctly inhibit the permeation of HUVEC cells into the lower chamber...
February 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28230282/ablation-of-cyclophilin-d-results-in-an-activation-of-fak-akt-and-erk-pathways-in-the-mouse-heart
#2
Jelena Klawitter, Tamas Seres, Alexander Pennington, Jonathan-Thomas Beatty, Jost Klawitter, Uwe Christians
Cyclophilin D (CypD) is a mitochondrial chaperone that regulates the mitochondrial permeability transition pore. Metabolically, deletion of Ppif (the gene encoding CypD) in mice is associated with elevated levels of mitochondrial matrix Ca(2+) that leads to increased glucose as relative to fatty acid oxidation. Here, we characterized the adaptive mechanisms involved in the regulation of glucose metabolism including the regulation of Akt and ERK kinases that we evaluated by Western blot analysis of Ppif-/-in comparison to wild type (WT) mouse hearts...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28225063/targeted-inhibition-of-focal-adhesion-kinase-attenuates-cardiac-fibrosis-and-preserves-heart-function-in-adverse-cardiac-remodeling
#3
Jie Zhang, Guangpu Fan, Hui Zhao, Zhiwei Wang, Fei Li, Peide Zhang, Jing Zhang, Xu Wang, Wei Wang
Cardiac fibrosis in post-myocardial infarction (MI), seen in both infarcted and non-infarcted myocardium, is beneficial to the recovery of heart function. But progressively pathological fibrosis impairs ventricular function and leads to poor prognosis. FAK has recently received attention as a potential mediator of fibrosis, our previous study reported that pharmacological inhibition of FAK can attenuate cardiac fibrosis in post MI models. However, the long-term effects on cardiac function and adverse cardiac remodelling were not clearly investigated...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223935/morus-alba-leaf-lectin-mll-sensitizes-mcf-7-cells-to-anoikis-by-inhibiting-fibronectin-mediated-integrin-fak-signaling-through-ras-and-activation-of-p-38-mapk
#4
Jayaram Saranya, Ganesan Shilpa, Kozhiparambil G Raghu, Sulochana Priya
Lectins are a unique class of carbohydrate binding proteins/glycoproteins, and many of them possess anticancer properties. They can induce cell cycle arrest and apoptosis, inhibit protein synthesis, telomerase activity and angiogenesis in cancer cells. In the present study, we have demonstrated the effect of Morus alba leaf lectin (MLL) on anoikis induction in MCF-7 cells. Anoikis induction in cancer cells has a significant role in preventing early stage metastasis. MLL treatment in monolayers of MCF-7 cells caused significant detachment of cells in a time and concentration dependent manner...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28223821/asparaginyl-endopeptidase-improves-the-resistance-of-microtubule-targeting-drugs-in-gastric-cancer-through-iqgap1-modulating-the-egfr-jnk-erk-signaling-pathway
#5
Yuehong Cui, Qian Li, Hong Li, Yan Wang, Hongshan Wang, Weidong Chen, Shangmin Zhang, Jian Cao, Tianshu Liu
PURPOSE: In recent years, understanding of the role of asparaginyl endopeptidase (AEP) in tumorigenesis has steadily increased. In this study, we investigated whether AEP expression correlates with sensitivity to chemotherapeutic drugs in gastric cancer and explored the mechanism. PATIENTS AND METHODS: AEP expression in the serum of patients' peripheral blood was measured by enzyme-linked immunosorbent assay. Patient survival time was evaluated using univariate and multivariate analyses...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28223426/resistance-mechanism-against-trastuzumab-in-her2-positive-cancer-cells-and-its-negation-by-src-inhibition
#6
Mei Hua Jin, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh
Trastuzumab in combination with chemotherapy is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancers. Several resistance mechanisms against anti-HER2 therapy have been proposed. Src activation has been suggested to be responsible for the resistance of HER2-positive breast cancer. In our study, we generated four trastuzumab-resistant (HR) cancer cell lines from HER2-amplified gastric and biliary tract cancer cell lines (SNU-216, NCI-N87, SNU-2670, and SNU-2773)...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28222177/phospholipid-binding-to-the-fak-catalytic-domain-impacts-function
#7
Jessica E Hall, Michael D Schaller
Focal adhesion kinase is an essential nonreceptor tyrosine kinase that plays an important role in development, in homeostasis and in the progression of human disease. Multiple stimuli activate FAK, which requires a change in structure from an autoinhibited to activated conformation. In the autoinhibited conformation the FERM domain associates with the catalytic domain of FAK and PI(4,5)P2 binding to the FERM domain plays a role in the release of autoinhibition, activating the enzyme. An in silico model of FAK/PI(4,5)P2 interaction suggests that residues on the catalytic domain interact with PI(4,5)P2, in addition to the known FERM domain PI(4,5)P2 binding site...
2017: PloS One
https://www.readbyqxmd.com/read/28214467/paxillin-a-crossroad-in-pathological-cell-migration
#8
REVIEW
Ana María López-Colomé, Irene Lee-Rivera, Regina Benavides-Hidalgo, Edith López
Paxilllin is a multifunctional and multidomain focal adhesion adapter protein which serves an important scaffolding role at focal adhesions by recruiting structural and signaling molecules involved in cell movement and migration, when phosphorylated on specific Tyr and Ser residues. Upon integrin engagement with extracellular matrix, paxillin is phosphorylated at Tyr31, Tyr118, Ser188, and Ser190, activating numerous signaling cascades which promote cell migration, indicating that the regulation of adhesion dynamics is under the control of a complex display of signaling mechanisms...
February 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28213973/transforming-growth-factor-%C3%AE-induces-bone-marrow-mesenchymal-stem-cell-migration-via-noncanonical-signals-and-n-cadherin
#9
Maria Jose Dubon, Jinyeong Yu, Sanghyuk Choi, Ki-Sook Park
Transforming growth factor-beta (TGF-β) induces the migration and mobilization of bone marrow-derived mesenchymal stem cells (BM-MSCs) to maintain bone homeostasis during bone remodeling and facilitate the repair of peripheral tissues. Although many studies have reported the mechanisms through which TGF-β mediates the migration of various types of cells, including cancer cells, the intrinsic cellular mechanisms underlying cellular migration and mobilization of BM-MSCs mediated by TGF-β are unclear. In this study, we showed that TGF-β activated noncanonical signaling molecules, such as Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and p38, via TGF-β type I receptor in human BM-MSCs and murine BM-MSC-like ST2 cells...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28213315/focal-adhesion-kinase-signaling-in-unexpected-places
#10
REVIEW
Elizabeth G Kleinschmidt, David D Schlaepfer
Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase first identified at extracellular matrix and integrin receptor cell adhesion sites and is a key regulator of cell movement. FAK is activated by a variety of stimuli. Herein, we discuss advances in conformational-associated FAK activation and dimerization mechanisms. Additionally, new roles have emerged for FAK signaling at cell adhesions, adherens junctions, endosomes, and the nucleus. In light of these new findings, we review how FAK activation at these sites is connected to the regulation of integrin recycling-activation, vascular permeability, cell survival, and transcriptional regulation, respectively...
February 14, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28209916/diabetic-concentrations-of-metformin-inhibit-platelet-mediated-ovarian-cancer-cell-progression
#11
Rafaela Erices, Sofía Cubillos, Raúl Aravena, Felice Santoro, Monica Marquez, Renan Orellana, Carolina Ramírez, Pamela González, Patricia Fuenzalida, María Loreto Bravo, Bárbara Oliva, Sumie Kato, Carolina Ibañez, Jorge Brañes, Erasmo Bravo, Catalina Alonso, Karen García, Clemente Arab, Vicente A Torres, Alejandro S Godoy, Jaime Pereira, Galdo Bustos, Julio Cesar Cardenas, Mauricio A Cuello, Gareth I Owen
Clinical studies have suggested a survival benefit in ovarian cancer patients with type 2 diabetes mellitus taking metformin, however the mechanism by which diabetic concentrations of metformin could deliver this effect is still poorly understood. Platelets not only represent an important reservoir of growth factors and angiogenic regulators, they are also known to participate in the tumor microenvironment implicated in tumor growth and dissemination. Herein, we investigated if diabetic concentrations of metformin could impinge upon the previously reported observation that platelet induces an increase in the tube forming capacity of endothelial cells (angiogenesis) and upon ovarian cancer cell aggressiveness...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28204814/fisetin-regulates-astrocyte-migration-and-proliferation-in%C3%A2-vitro
#12
Nan Wang, Fang Yao, Ke Li, Lanlan Zhang, Guo Yin, Mingjun Du, Bingyi Wu
Fisetin (3,3',4',7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte migration in a scratch-wound assay and diminished the phosphorylation of focal adhesion kinase (FAK; Tyr576/577 and paxillin (Tyr118)...
February 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202937/focal-adhesion-kinase-activity-is-required-for-actomyosin-contractility-based-invasion-of-cells-into-dense-3d-matrices
#13
Claudia T Mierke, Tony Fischer, Stefanie Puder, Tom Kunschmann, Birga Soetje, Wolfgang H Ziegler
The focal adhesion kinase (FAK) regulates the dynamics of integrin-based cell adhesions important for motility. FAK's activity regulation is involved in stress-sensing and focal-adhesion turnover. The effect of FAK on 3D migration and cellular mechanics is unclear. We analyzed FAK knock-out mouse embryonic fibroblasts and cells expressing a kinase-dead FAK mutant, R454-FAK, in comparison to FAK wild-type cells. FAK knock-out and FAK(R454/R454) cells invade dense 3D matrices less efficiently. These results are supported by FAK knock-down in wild-type fibroblasts and MDA-MB-231 human breast cancer cells showing reduced invasiveness...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194552/a-novel-synthetic-small-molecule-yf-452-inhibits-tumor-growth-through-antiangiogenesis-by-suppressing-vegf-receptor-2-signaling
#14
Yongrui Liu, Yuan He, Feifei Yang, Xiaonan Cong, Jinhua Wang, Shihong Peng, Dan Gao, Weifang Wang, Liping Lan, Xuexiang Ying, Mingyao Liu, Yihua Chen, Zhengfang Yi
Tumor angiogenesis is characterized by abnormal vessel morphology, endowing tumor with highly hypoxia and unresponsive toward treatment. To date, mounting angiogenic factors have been discovered as therapeutic targets in antiangiogenic drug development. Among them, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors exerts potent antiangiogenic activity in tumor therapy. Therefore, it may provide a valid strategy for cancer treatment through targeting the tumor angiogenesis via VEGFR2 pathway...
February 13, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28184941/combined-effects-of-furanodiene-and-doxorubicin-on-the-migration-and-invasion-of-mda-mb-231-breast-cancer-cells-in-vitro
#15
Zhang-Feng Zhong, Wen Tan, Ke Tian, Hua Yu, Wen-An Qiang, Yi-Tao Wang
Furanodiene is one of the major bioactive components isolated from the natural product of the plant, Curcuma wenyujin Y.H. Chen et C. Ling. Furanodiene has been found to exert anticancer effects in various types of cancer cell lines, as well as exhibit antimetastatic activities. However, the antimetastatic capacity of furanodiene in combination with the common chemotherapy drug doxorubicin has not been investigated. We found that doxorubicin at a non-toxic concentration induced cell migration and cell invasion in highly metastatic breast cancer cells...
February 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28182100/semaphorin-3a-increases-fak-phosphorylation-at-focal-adhesions-to-modulate-mda-mb-231-cell-migration-and-spreading-on-different-substratum-concentrations
#16
Scott Gehler, Frances V Compere, Alex M Miller
Interactions between integrin-mediated adhesions and the extracellular matrix (ECM) are important regulators of cell migration and spreading. However, mechanisms by which extracellular ligands regulate cell migration and spreading in response to changes in substratum concentration are not well understood. Semaphorin 3A (Sema3A) has been shown to inhibit cell motility and alter integrin signaling in various cell types. We propose that Sema3A alters focal adhesions to modulate breast carcinoma cell migration and spreading on substrata coated with different concentrations of ECM...
2017: International Journal of Breast Cancer
https://www.readbyqxmd.com/read/28168016/deletion-of-the-ste20-like-kinase-slk-in-skeletal-muscle-results-in-a-progressive-myopathy-and-muscle-weakness
#17
Benjamin R Pryce, Khalid N Al-Zahrani, Sébastien Dufresne, Natalya Belkina, Cédrik Labrèche, Genaro Patino-Lopez, Jérôme Frenette, Stephen Shaw, Luc A Sabourin
BACKGROUND: The Ste20-like kinase, SLK, plays an important role in cell proliferation and cytoskeletal remodeling. In fibroblasts, SLK has been shown to respond to FAK/Src signaling and regulate focal adhesion turnover through Paxillin phosphorylation. Full-length SLK has also been shown to be essential for embryonic development. In myoblasts, the overexpression of a dominant negative SLK is sufficient to block myoblast fusion. METHODS: In this study, we crossed the Myf5-Cre mouse model with our conditional SLK knockout model to delete SLK in skeletal muscle...
2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28167607/a-key-regulator-of-cell-adhesion-identification-and-characterization-of-important-n-glycosylation-sites-on-integrin-%C3%AE-5-for-cell-migration
#18
Qinglei Hang, Tomoya Isaji, Sicong Hou, Yuqin Wang, Tomohiko Fukuda, Jianguo Gu
The N-glycosylation of integrin α5β1 is thought to control many fundamental aspects of cell behavior, including cell adhesion and migration. However, the mechanism of how N-glycans function remains largely obscure. Here, we used a loss-of-function approach. The wild-type (WT) and N-glycosylation mutant integrin α5, S3-5 (sites 3, 4 and 5), which contains fewer N-glycans, were stably reconstituted in α5-knock-out cancer cells. We found that the migration ability of the S3-5 cells was decreased by comparison with the WT...
February 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28165007/fak-signalling-controls-insulin-sensitivity-through-regulation-of-adipocyte-survival
#19
Cynthia T Luk, Sally Yu Shi, Erica P Cai, Tharini Sivasubramaniyam, Mansa Krishnamurthy, Jara J Brunt, Stephanie A Schroer, Daniel A Winer, Minna Woo
Focal adhesion kinase (FAK) plays a central role in integrin signalling, which regulates growth and survival of tumours. Here we show that FAK protein levels are increased in adipose tissue of insulin-resistant obese mice and humans. Disruption of adipocyte FAK in mice or in 3T3 L1 cells decreases adipocyte survival. Adipocyte-specific FAK knockout mice display impaired adipose tissue expansion and insulin resistance on prolonged metabolic stress from a high-fat diet or when crossed on an obese db/db or ob/ob genetic background...
February 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28161490/structural-analysis-of-ribosomal-rack1-and-its-role-in-translational-control
#20
Maja Holch Nielsen, Rasmus Kock Flygaard, Lasse Bohl Jenner
Receptor for Activated C-Kinase 1 (RACK1) belongs to the WD40 family of proteins, known to act as scaffolding proteins in interaction networks. Accordingly, RACK1 is found to have numerous interacting partners ranging from kinases and signaling proteins to membrane bound receptors and ion channels. Interestingly, RACK1 has also been identified as a ribosomal protein present in all eukaryotic ribosomes. Structures of eukaryotic ribosomes have shown RACK1 to be located at the back of the head of the small ribosomal subunit...
February 1, 2017: Cellular Signalling
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