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https://www.readbyqxmd.com/read/28636424/fluid-shear-stress-regulates-hepg2-cell-migration-though-time-dependent-integrin-signaling-cascade
#1
Hongchi Yu, Yang Shen, Jingsi Jin, Yingying Zhang, Tang Feng, Xiaoheng Liu
Hepatocellular carcinoma (HCC) is a subtype of malignant liver cancer with poor prognosis and limited treatment options. It is noteworthy that mechanical forces in tumor microenvironment play a pivotal role in mediating the behaviors and functions of tumor cells. As an instrumental type of mechanical forces in vivo, fluid shear stress (FSS) has been reported having potent physiologic and pathologic effects on cancer progression. However, the time-dependent mechanochemical transduction in HCC induced by FSS remains unclear...
June 21, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28626446/gnrh-induces-erk-dependent-bleb-formation-in-gonadotrope-cells-involving-recruitment-of-members-of-a-gnrh-receptor-associated-signalosome-to-the-blebs
#2
Liat Rahamim-Ben Navi, Anna Tsukerman, Alona Feldman, Philippa Melamed, Melanija Tomić, Stanko S Stojilkovic, Ulrich Boehm, Rony Seger, Zvi Naor
We have previously described a signaling complex (signalosome) associated with the GnRH receptor (GnRHR). We now report that GnRH induces bleb formation in the gonadotrope-derived LβT2 cells. The blebs appear within ~2 min at a turnover rate of ~2-3 blebs/min and last for at least 90 min. Formation of the blebs requires active ERK1/2 and RhoA-ROCK but not active c-Src. Although the following ligands stimulate ERK1/2 in LβT2 cells: EGF > GnRH > PMA > cyclic adenosine monophosphate (cAMP), they produced little or no effect on bleb formation as compared to the robust effect of GnRH (GnRH > PMA > cAMP > EGF), indicating that ERK1/2 is required but not sufficient for bleb formation possibly due to compartmentalization...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28620171/mechanical-stability-of-talin-rod-controls-cell-migration-and-substrate-sensing
#3
Rolle Rahikainen, Magdaléna von Essen, Markus Schaefer, Lei Qi, Latifeh Azizi, Conor Kelly, Teemu O Ihalainen, Bernhard Wehrle-Haller, Martin Bastmeyer, Cai Huang, Vesa P Hytönen
Cells adhere to the surrounding tissue and probe its mechanical properties by forming cell-matrix adhesions. Talin is a critical adhesion protein and participates in the transmission of mechanical signals between extracellular matrix and cell cytoskeleton. Force induced unfolding of talin rod subdomains has been proposed to act as a cellular mechanosensor, but so far evidence linking their mechanical stability and cellular response has been lacking. Here, by utilizing computationally designed mutations, we demonstrate that stepwise destabilization of the talin rod R3 subdomain decreases cellular traction force generation, which affects talin and vinculin dynamics in cell-matrix adhesions and results in the formation of talin-rich but unstable adhesions...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611383/integrin-%C3%AE-2%C3%AE-1-in-nonactivated-conformation-can-induce-focal-adhesion-kinase-signaling
#4
Maria Salmela, Johanna Jokinen, Silja Tiitta, Pekka Rappu, R Holland Cheng, Jyrki Heino
Conformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of α2β1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, α2E336A, in the α2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592633/the-phospho-caveolin-1-scaffolding-domain-dampens-force-fluctuations-in-focal-adhesions-and-promotes-cancer-cell-migration
#5
Fanrui Meng, Sandeep Saxena, Youtao Liu, Bharat Joshi, Timothy H Wong, Jay Shankar, Leonard J Foster, Pascal Bernatchez, Ivan R Nabi
Caveolin-1 (Cav1), a major Src kinase substrate phosphorylated on tyrosine-14 (Y14), contains the highly-conserved membrane-proximal caveolin scaffolding domain (CSD; amino acids 82-101). Here we show, using CSD mutants (F92A/V94A) and membrane-permeable CSD competing peptides, that Src kinase-dependent pY14Cav1 regulation of focal adhesion protein stabilization, focal adhesion tension and cancer cell migration is CSD-dependent. Quantitative proteomic analysis of Cav1-GST (1-101 amino acids) pulldowns showed 6-fold increased binding of vinculin and, to a lesser extent, α-actinin, talin and filamin, to phosphomimetic Cav1Y14D relative to non-phosphorylatable Cav1Y14F...
June 7, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28576970/low-intensity-pulsed-ultrasound-lipus-promotes-cell-motility-through-vinculin-controlled-rac1-gtpase-activity
#6
Paul Atherton, Franziska Lausecker, Andrew Harrison, Christoph Ballestrem
Low Intensity Pulsed Ultrasound (LIPUS) is a therapy used clinically to promote healing. Using live cell imaging we show that LIPUS stimulation, acting through integrin-mediated cell-matrix adhesions, rapidly induces Rac activation associated with dramatic actin cytoskeleton rearrangements. Our study demonstrates that the mechanosensitive focal adhesion (FA) protein vinculin and both Focal Adhesion Kinase (FAK) and Rab5 have key roles in regulating these effects. Inhibiting the link of vinculin to the actin-cytoskeleton abolished LIPUS sensing...
June 2, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28575979/live-cell-biosensor-for-assessment-of-adhesion-qualities-of-biomaterials
#7
Svetlana I Ivanova, Stoyan Chakarov, Albena Momchilova, Roumen Pankov
The present study describes a live-cell biosensor, suitable for general evaluation of adhesion qualities of different substrates. It is based on NIH/3T3 fibroblast cell line stably expressing fusion fluorescently tagged proteins mCherry-vinculin and GFP-tensin as quantifiable markers for assessment not only of focal but also of fibrillar contacts. Four measurable parameters - spreading, polarization and development of focal and fibrillar adhesions were used to standardize the adhesion of biosensor cells after plating on five substrates of natural origin - fibronectin, vitronectin, laminin-111, laminin-521 and collagen type I...
September 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28554775/zonula-occludens-2-regulates-rho-proteins-activity-and-the-development-of-epithelial-cytoarchitecture-and-barrier-function
#8
Arturo Raya-Sandino, Alejandro Castillo-Kauil, Alaide Domínguez-Calderón, Lourdes Alarcón, David Flores-Benitez, Francisco Cuellar-Perez, Bruno López-Bayghen, Bibiana Chávez-Munguía, José Vázquez-Prado, Lorenza González-Mariscal
Silencing Zonula occludens 2 (ZO-2), a tight junctions (TJ) scaffold protein, in epithelial cells (MDCK ZO-2 KD) triggers: 1) Decreased cell to substratum attachment, accompanied by reduced expression of claudin-7 and integrin β1, and increased vinculin recruitment to focal adhesions and stress fibers formation; 2) Lowered cell-cell aggregation and appearance of wider intercellular spaces; 3) Increased RhoA/ROCK activity, mediated by GEF-HI recruitment to cell borders by cingulin; 4) Increased Cdc42 activity, mitotic spindle disorientation and the appearance of cysts with multiple lumens; 5) Increased Rac and cofilin activity, multiple lamellipodia formation and random cell migration but increased wound closure; 6) Diminished cingulin phosphorylation and disappearance of planar network of microtubules at the TJ region; and 7) Increased transepithelial electrical resistance at steady state, coupled to an increased expression of ZO-1 and claudin-4 and a decreased expression of claudin-2 and paracingulin...
May 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28552713/mass-spectrometric-detection-combined-with-bioinformatic-analysis-identified-possible-protein-markers-and-key-pathways-associated-with-bladder-cancer
#9
Ziyu Wu, Sugui Wang, Fujin Jiang, Qiang Li, Chao Wang, Huanqiang Wang, Wei Zhang, Peng Xue, Shoulin Wang
We aimed to find possible protein markers and key pathways related to bladder cancer. In total, we extracted three bladder cancer tissues and three paracancerous tissues from Jiangsu Provincial People's Hospital Urology Department, and performed mass spectrometric detection with Q Exactive. Subsequently, we screened the differentially expressed proteins in the disease group and the normal group using the LIMMA package, and performed functional enrichment analyses using DAVID. Further, we constructed protein-protein interaction (PPI) networks with Cytoscape software, and analyzed modules with ClusterONE...
May 25, 2017: Gene
https://www.readbyqxmd.com/read/28549588/graphene-modified-titanium-alloy-promote-the-adhesion-proliferation-and-osteogenic-differentiation-of-bone-marrow-stromal-cells
#10
Kewen Li, Jinhong Yan, Chunhui Wang, Long Bi, Qi Zhang, Yisheng Han
We studied the effects of graphene coating on improving the biological activity of a titanium alloy (Ti6Al4V) widely used in hip and knee joint replacements. The experiments included immunofluorescence staining for observing cellular adhesion, Cell Counting Kit-8 (CCK-8) for evaluating cellular proliferation and reverse transcription-polymerase chain reaction (RT-PCR) for detecting the differentiation of bone marrow stromal cells on different scaffolds. The results showed that G-Ti6Al4V exhibited a higher mean integrated optical density (IOD) for vinculin and resulted in a higher cell proliferation rate and higher osteoblast-specific gene transcription levels...
May 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28540429/identification-of-markers-for-quiescent-pancreatic-stellate-cells-in-the-normal-human-pancreas
#11
Michael Friberg Bruun Nielsen, Michael Bau Mortensen, Sönke Detlefsen
Pancreatic stellate cells (PSCs) play a central role as source of fibrogenic cells in pancreatic cancer and chronic pancreatitis. In contrast to quiescent hepatic stellate cells (qHSCs), a specific marker for quiescent PSCs (qPSCs) that can be used in formalin-fixed and paraffin embedded (FFPE) normal human pancreatic tissue has not been identified. The aim of this study was to identify a marker enabling the identification of qPSCs in normal human FFPE pancreatic tissue. Immunohistochemical (IHC), double-IHC, immunofluorescence (IF) and double-IF analyses were carried out using a tissue microarray consisting of cores with normal human pancreatic tissue...
May 25, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28499977/human-neural-stem-progenitor-cells-derived-from-the-olfactory-epithelium-express-the-trkb-receptor-and-migrate-in-response-to-bdnf
#12
Leonardo Ortiz-López, Jorge Julio González-Olvera, Nelly Maritza Vega-Rivera, Maria García-Anaya, Ana Karen Carapia-Hernández, Julio César Velázquez-Escobar, Gerardo Bernabé Ramírez-Rodríguez
Neurogenesis constitutively occurs in the olfactory epithelium of mammals, including humans. The fact that new neurons in the adult olfactory epithelium derive from resident neural stem/progenitor cells suggests a potential use for these cells in studies of neural diseases, as well as in neuronal cell replacement therapies. In this regard, some studies have proposed that the human olfactory epithelium is a source of neural stem/progenitor cells for autologous transplantation. Although these potential applications are interesting, it is important to understand the cell biology and/or whether human neural stem/progenitor cells in the olfactory epithelium sense external signals, such as brain-derived neurotrophic factor (BDNF), that is also found in other pro-neurogenic microenvironments...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28498477/identification-of-candidate-substrates-of-ubiquitin-specific-protease-13-using-2d-dige
#13
Jianmin Wang, Yingli Liu, Lijuan Tang, Sufen Qi, Yingjun Mi, Dianwu Liu, Qingbao Tian
The present study aimed to identify candidate substrates of ubiquitin-specific protease (USP)13 using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). USP13 is a well-characterized member of the USP family, which regulates diverse cellular functions by cleaving ubiquitin from ubiquitinated protein substrates. However, existing studies indicate that USP13 has no detectable hydrolytic activity in vitro. This finding implies that USP13 likely has different substrate specificity. In this study, a USP cleavage assay was performed using two different types of model substrates (glutathione S-transferase-Ub52 and ubiquitin-β-galactosidase) to detect the deubiquitinating enzyme (DUB) activity of USP13...
May 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28497946/nanopillar-surface-topology-promotes-cardiomyocyte-differentiation-through-cofilin-mediated-cytoskeleton-rearrangement
#14
Ha-Rim Seo, Hyung Joon Joo, Dae Hwan Kim, Long-Hui Cui, Seung-Cheol Choi, Jong-Ho Kim, Sung Woo Cho, Kyu Back Lee, Do-Sun Lim
Nanoscaled surface patterning is an emerging potential method of directing the fate of stem cells. We adopted nanoscaled pillar gradient patterned cell culture plates with three diameter gradients [280-360 (GP 280/360), 200-280 (GP 200/280), and 120-200 nm (GP 120/200)] and investigated their cell fate-modifying effect on multipotent fetal liver kinase 1-positive mesodermal precursor cells (Flk1(+) MPCs) derived from embryonic stem cells. We observed increased cell proliferation and colony formation of the Flk1(+) MPCs on the nanopattern plates...
May 12, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28494959/mechanosensitive-conformation-of-vinculin-regulates-its-binding-to-mapk1
#15
Kiavash Garakani, Hengameh Shams, Mohammad R K Mofrad
Extracellular matrix stiffness sensing by living cells is known to play a major role in a variety of cell mechanobiological processes, such as migration and differentiation. Various membrane and cytoplasmic proteins are involved in transmitting and transducing environmental signals to biochemical cascades. Protein kinases play a key role in regulating the activity of focal adhesion proteins. Recently, an interaction between mitogen-activated protein kinase (MAPK1) and vinculin was experimentally shown to mediate this process...
May 9, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28485208/the-distribution-of-vinculin-to-lipid-rafts-plays-an-important-role-in-sensing-stiffness-of-extracellular-matrix
#16
Ayaka Ichikawa Nagasato, Hiroshi Yamashita, Michinori Matsuo, Kazumitsu Ueda, Noriyuki Kioka
Extracellular matrix (ECM) stiffness regulates cell differentiation, survival, and migration. Our previous study has shown that the interaction of the focal adhesion protein vinculin with vinexin α plays a critical role in sensing ECM stiffness and regulating stiffness-dependent cell migration. However, the mechanism how vinculin-vinexin α interaction affects stiffness-dependent cell migration is unclear. Lipid rafts are membrane microdomains that are known to affect ECM-induced signals and cell behaviors...
June 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28476046/cell-matrix-adhesions-in-cancer-the-proteins-that-form-the-glue
#17
REVIEW
Mazvita Maziveyi, Suresh K Alahari
The main purposes of Integrin-mediated cell contacts are to interpret bi-directional signals between the extracellular environment and intracellular proteins, as well as, anchor the cell to a matrix. Many cell adhesion molecules have been discovered with a wide spectrum of responsibilities, including recruiting, activating, elongating, and maintaining. This review will perlustrate some of the key incidences that precede focal adhesion formation. Tyrosine phosphorylation is a key signaling initiation event that leads to the recruitment of multiple proteins to focal adhesion sites...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28468976/effects-of-substrate-stiffness-and-actomyosin-contractility-on-coupling-between-force-transmission-and-vinculin-paxillin-recruitment-at-single-focal-adhesions
#18
Dennis W Zhou, Ted T Lee, Shinuo Weng, Jianping Fu, Andrés J García
Focal adhesions (FAs) regulate force transfer between the cytoskeleton and ECM-integrin complexes. We previously showed that vinculin regulates force transmission at FAs. Vinculin residence time in FAs correlated with applied force, supporting a mechanosensitive model in which forces stabilize vinculin's active conformation to promote force transfer. In the present study, we examined the relationship between traction force and vinculin-paxillin localization to single FAs in the context of substrate stiffness and actomyosin contractility...
May 3, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28460304/adhesion-profile-and-differentiation-capacity-of-human-adipose-tissue-derived-mesenchymal-stem-cells-grown-on-metal-ion-zn-ag-and-cu-doped-hydroxyapatite-nano-coated-surfaces
#19
R Beklem Bostancioglu, Mevlut Gurbuz, Ayse Gul Akyurekli, Aydin Dogan, A Savas Koparal, A Tansu Koparal
Accelerated Mesenchymal Stem Cells (MSCs) condensation and robust MSC-matrix and MSC-MSC interactions on nano-surfaces may provide critical factors contributing to such events, likely through the orchestrated signal cascades and cellular events modulated by the extracellular matrix. In this study, human adipose tissue derived mesenchymal stem cells (hMSC)', were grown on metal ion (Zn, Ag and Cu) doped hydroxyapatite (HAP) nano-coated surfaces. These metal ions are known to have different chemical and surface properties; therefore we investigated their respective contributions to cell viability, cellular behavior, osteogenic differentiation capacity and substrate-cell interaction...
April 13, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28454435/15-deoxy-%C3%AE-12-14-prostaglandin-j2-inhibits-migration-of-human-thyroid-carcinoma-cells-by-disrupting-focal-adhesion-complex-and-adherens-junction
#20
Ya-Chieh Wu, Yun-Ting Jhao, Yu-Chen Cheng, Ying Chen
Metastasis is frequently observed in human follicular thyroid carcinoma. The present study investigated the peroxisome proliferator-activated receptor γ agonist, 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ2), and its effect on the migration of CGTH W-2 human thyroid carcinoma cells. 15d-PGJ2 decreased the survival rate of CGTH W-2 cells in a dose-dependent manner. The Transwell migration assay demonstrated that 15d-PGJ2 reduced the migration rate of CGTH W-2 cells by 35% following treatment with 30 µM 15d-PGJ2 compared with control cells...
April 2017: Oncology Letters
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