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https://www.readbyqxmd.com/read/28319045/akt-mediated-stabilization-of-histone-methyltransferase-whsc1-promotes-prostate-cancer-metastasis
#1
Ni Li, Wei Xue, Huairui Yuan, Baijun Dong, Yufeng Ding, Yongfeng Liu, Min Jiang, Shan Kan, Tongyu Sun, Jiale Ren, Qiang Pan, Xiang Li, Peiyuan Zhang, Guohong Hu, Yan Wang, Xiaoming Wang, Qintong Li, Jun Qin
Loss of phosphatase and tensin homolog (PTEN) and activation of the PI3K/AKT signaling pathway are hallmarks of prostate cancer (PCa). However, these alterations alone are insufficient for cells to acquire metastatic traits. Here, we have shown that the histone dimethyl transferase WHSC1 critically drives indolent PTEN-null tumors to become metastatic PCa. In a PTEN-null murine PCa model, WHSC1 overexpression in prostate epithelium cooperated with Pten deletion to produce a metastasis-prone tumor. Conversely, genetic ablation of Whsc1 prevented tumor progression in PTEN-null mice...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28317937/identification-of-cancer-associated-missense-mutations-in-hace1-that-impair-cell-growth-control-and-rac1-ubiquitylation
#2
Emilie Andrio, Romain Lotte, Daniel Hamaoui, Jacqueline Cherfils, Anne Doye, Mads Daugaard, Poul H Sorensen, Frédéric Bost, Raymond Ruimy, Amel Mettouchi, Emmanuel Lemichez
The E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase Rac1 to target it to proteasomal degradation. Whether and how the activity of HACE1 is regulated by the N-terminal ankyrin (ANK) and the middle (MID) domains is ill defined. Here, we identified in the version 64 of the Catalogue of Somatic Mutations in Cancer (COSMIC) 13 missense mutations of hace1 located outside the HECT domain, and found that all lead to defective control of cell proliferation...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302906/distinct-focal-adhesion-protein-modules-control-different-aspects-of-mechanotransduction
#3
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/28301477/fragility-of-foot-process-morphology-in-kidney-podocytes-arises-from-chaotic-spatial-propagation-of-cytoskeletal-instability
#4
Cibele V Falkenberg, Evren U Azeloglu, Mark Stothers, Thomas J Deerinck, Yibang Chen, John C He, Mark H Ellisman, James C Hone, Ravi Iyengar, Leslie M Loew
Kidney podocytes' function depends on finger-like projections (foot processes) that interdigitate with those from neighboring cells to form the glomerular filtration barrier. The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes. We determined how imbalances in regulation of actin cytoskeletal dynamics could result in pathological morphology. We obtained 3-D electron microscopy images of podocytes and used quantitative features to build dynamical models to investigate how regulation of actin dynamics within foot processes controls local morphology...
March 16, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28298485/mcak-mediated-regulation-of-endothelial-cell-microtubule-dynamics-is-mechano-sensitive-to-myosin-ii-contractility
#5
Lauren D'Angelo, Nicole M Myer, Kenneth A Myers
Compliance and dimensionality mechanosensing, the processes by which cells sense the physical attributes of the extracellular environment (ECM), are known to drive cell branching and shape change largely through a myosin-II-mediated reorganization of the actin and microtubule (MT) cytoskeletons. Subcellular regulation of MT dynamics is spatially controlled through a Rac1-Aurora-A kinase pathway that locally inhibits the MT depolymerizing activity of MCAK, thereby promoting leading-edge MT growth and cell polarization...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28296262/the-c-terminal-region-of-the-major-outer-sheath-protein-msp-of-treponema-denticola-inhibits-neutrophil-chemotaxis
#6
Megan M Jones, Stephen T Vanyo, Michelle B Visser
Treponema denticola is an oral spirochete strongly associated with severe periodontal disease. A prominent virulence factor, the major outer sheath protein (Msp), disorients neutrophil chemotaxis by altering the cellular phosphoinositide balance, leading to impairment of downstream chemotactic events including actin rearrangement, Rac1 activation and Akt activation in response to chemoattractant stimulation. The specific regions of Msp responsible for interactions with neutrophils remain unknown. In this study, we investigated the inhibitory effect of truncated Msp regions on neutrophil chemotaxis and associated signaling pathways...
March 13, 2017: Molecular Oral Microbiology
https://www.readbyqxmd.com/read/28289332/pi3k%C3%AE-isoform-dependent-activation-of-rhoa-regulates-wnt5a-induced-osteosarcoma-cell-migration
#7
Ailiang Zhang, Ting Yan, Kun Wang, Zhihui Huang, Jinbo Liu
BACKGROUND: We have reported that the phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway mediated Wnt5a-induced osteosarcoma cell migration. However, the signaling pathways regulating Wnt5a/PI3K/Akt-mediated cell migration remains poorly defined in osteosarcoma cells. METHODS: We evaluated the activations of RhoA, Rac1 and Cdc42 in osteosarcoma MG-63 and U2OS cells with small G-protein activation assay. Boyden chamber assays were used to confirm the migration of cells transfected indicated constructs or siRNA specific against RhoA...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28288135/targeting-lyn-regulates-snail-family-shuttling-and-inhibits-metastasis
#8
D Thaper, S Vahid, K M Nip, I Moskalev, X Shan, S Frees, M E Roberts, K Ketola, K W Harder, C Gregory-Evans, J L Bishop, A Zoubeidi
The acquisition of an invasive phenotype by epithelial cells occurs through a loss of cellular adhesion and polarity, heralding a multistep process that leads to metastatic dissemination. Since its characterization in 1995, epithelial-mesenchymal transition (EMT) has been closely linked to the metastatic process. As a defining aspect of EMT, loss of cell adhesion through downregulation of E-cadherin is carried out by several transcriptional repressors; key among them the SNAI family of transcription factors...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28287395/p27-kip1-promotes-invadopodia-turnover-and-invasion-through-the-regulation-of-the-pak1-cortactin-pathway
#9
Pauline Jeannot, Ada Nowosad, Renaud T Perchey, Caroline Callot, Evangeline Bennana, Takanori Katsube, Patrick Mayeux, François Guillonneau, Stéphane Manenti, Arnaud Besson
p27(Kip1) (p27) is a cyclin-CDK inhibitor and negative regulator of cell proliferation. p27 also controls other cellular processes including migration and cytoplasmic p27 can act as an oncogene. Furthermore, cytoplasmic p27 promotes invasion and metastasis, in part by promoting epithelial to mesenchymal transition. Herein, we find that p27 promotes cell invasion by binding to and regulating the activity of Cortactin, a critical regulator of invadopodia formation. p27 localizes to invadopodia and limits their number and activity...
March 13, 2017: ELife
https://www.readbyqxmd.com/read/28287327/mechanism-of-cell-intrinsic-adaptation-to-adams-oliver-syndrome-gene-dock6-disruption-highlights-ubiquitin-like-modifier-isg15-as-a-regulator-of-rho-gtpases
#10
Berati Cerikan, Elmar Schiebel
DOCK6 is a RAC1/CDC42 guanine nucleotide exchange factor, however, little is known about its function and sub-cellular localization. DOCK6 regulates the balance between RAC1 and RHOA activity during cell adhesion and is important for CDC42-dependent mitotic chromosome alignment. Surprisingly, a cell intrinsic adaptation mechanism compensates for errors in these DOCK6 functions that arise as a consequence of prolonged DOCK6 depletion or complete removal in DOCK6 knockout cells. Down-regulation of the ubiquitin-like modifier ISG15 accounts for this adaptation...
February 23, 2017: Small GTPases
https://www.readbyqxmd.com/read/28286014/proteomics-based-network-analysis-characterizes-biological-processes-and-pathways-activated-by-preconditioned-mesenchymal-stem-cells-in-cardiac-repair-mechanisms
#11
Dario Di Silvestre, Francesca Brambilla, Giovanni Scardoni, Pietro Brunetti, Sara Motta, Marco Matteucci, Carlo Laudanna, Fabio A Recchia, Vincenzo Lionetti, Pierluigi Mauri
BACKGROUND: We have demonstrated that intramyocardial delivery of human mesenchymal stem cells preconditioned with a hyaluronan mixed ester of butyric and retinoic acid (MSCp(+)) is more effective in preventing the decay of regional myocardial contractility in a swine model of myocardial infarction (MI). However, the understanding of the role of MSCp(+) in proteomic remodeling of cardiac infarcted tissue is not complete. We therefore sought to perform a comprehensive analysis of the proteome of infarct remote (RZ) and border zone (BZ) of pigs treated with MSCp(+) or unconditioned stem cells...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28284862/investigation-on-cellular-uptake-and-pharmacodynamics-of-dock2-inhibitory-peptides-conjugated-with-cell-penetrating-peptides
#12
Yusuke Adachi, Kotaro Sakamoto, Tadashi Umemoto, Yasunori Fukuda, Akiyoshi Tani, Taiji Asami
Protein-protein interaction between dedicator of cytokinesis 2 (DOCK2) and Ras-related C3 botulinum toxin substrate 1 (Rac1) is an attractive intracellular target for transplant rejection and inflammatory diseases. Recently, DOCK2-selective inhibitory peptides have been discovered, and conjugation with oligoarginine cell-penetrating peptide (CPP) improved inhibitory activity in a cell migration assay. Although a number of CPPs have been reported, oligoarginine was only one example introduced to the inhibitory peptides...
February 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28279922/biomaterial-enabled-delivery-of-sdf-1%C3%AE-at-the-ventral-side-of-breast-cancer-cells-reveals-a-crosstalk-between-cell-receptors-to-promote-the-invasive-phenotype
#13
Xi Qiu Liu, Laure Fourel, Fabien Dalonneau, Rabia Sadir, Salome Leal, Hugues Lortat-Jacob, Marianne Weidenhaupt, Corinne Albiges-Rizo, Catherine Picart
The SDF-1α chemokine (CXCL12) is a potent bioactive chemoattractant known to be involved in hematopoietic stem cell homing and cancer progression. The associated SDF-1α/CXCR4 receptor signaling is a hallmark of aggressive tumors, which can metastasize to distant sites such as lymph nodes, lung and bone. Here, we engineered a biomimetic tumoral niche made of a thin and soft polyelectrolyte film that can retain SDF-1α to present it, in a spatially-controlled manner, at the ventral side of the breast cancer cells...
February 27, 2017: Biomaterials
https://www.readbyqxmd.com/read/28278510/autocrine-vegf-and-il-8-promote-migration-via-src-vav2-rac1-pak1-signaling-in-human-umbilical-vein-endothelial-cells
#14
Li Ju, Zhiwen Zhou, Bo Jiang, Yue Lou, Xirong Guo
BACKGROUND/AIMS: Pro-angiogenic factors VEGF and IL-8 play a major role in modulating the migratory potential of endothelial cells. The goal of this study was to investigate the effect of autocrine VEGF and IL-8 in the form of self-conditioned medium (CM) on human umbilical vein endothelial cells (HUVECs). METHODS: Enzyme-linked immunosorbent assay (ELISA) examined the automatic secretion of VEGF and IL-8 protein by HUVECs. Western blot, small interfering RNA (siRNA), pulldown and Transwell assays were used to explore the role and the mechanism of autocrine VEGF and IL-8 in migration of HUVECs...
March 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28277539/epidermal-rac1-regulates-the-dna-damage-response-and-protects-from-uv-light-induced-keratinocyte-apoptosis-and-skin-carcinogenesis
#15
Jayesh Deshmukh, Ruth Pofahl, Ingo Haase
Non-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far...
March 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28276928/plectin-deficiency-in-liver-cancer-cells-promotes-cell-migration-and-sensitivity-to-sorafenib-treatment
#16
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/28276699/p120-catenin-in-canonical-wnt-signaling
#17
Mireia Duñach, Beatriz Del Valle-Pérez, Antonio García de Herreros
Canonical Wnt signaling controls β-catenin protein stabilization, its translocation to the nucleus and the activation of β-catenin/Tcf-4-dependent transcription. In this review, we revise and discuss the recent results describing actions of p120-catenin in different phases of this pathway. More specifically, we comment its involvement in four different steps: (i) the very early activation of CK1ɛ, essential for Dvl-2 binding to the Wnt receptor complex; (ii) the internalization of GSK3 and Axin into multivesicular bodies, necessary for a complete stabilization of β-catenin; (iii) the activation of Rac1 small GTPase, required for β-catenin translocation to the nucleus; and (iv) the release of the inhibitory action caused by Kaiso transcriptional repressor...
March 3, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28274785/expression-of-rac1-alternative-3-utrs-is-a-cell-specific-mechanism-with-a-function-in-dendrite-outgrowth-in-cortical-neurons
#18
Sandra Oliveira Braz, Andrea Cruz, Andrea Lobo, Joana Bravo, Joana Moreira-Ribeiro, Isabel Pereira-Castro, Jaime Freitas, Joao B Relvas, Teresa Summavielle, Alexandra Moreira
The differential expression of mRNAs containing tandem alternative 3' UTRs, achieved by mechanisms of alternative polyadenylation and post-transcriptional regulation, has been correlated with a variety of cellular states. In differentiated cells and brain tissues there is a general use of distal polyadenylation signals, originating mRNAs with longer 3' UTRs, in contrast with proliferating cells and other tissues such as testis, where most mRNAs contain shorter 3' UTRs. Although cell type and state are relevant in many biological processes, how these mechanisms occur in specific brain cell types is still poorly understood...
March 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28273449/r-spondin1-controls-muscle-cell-fusion-through-dual-regulation-of-antagonistic-wnt-signaling-pathways
#19
Floriane Lacour, Elsa Vezin, C Florian Bentzinger, Marie-Claude Sincennes, Lorenzo Giordani, Arnaud Ferry, Robert Mitchell, Ketan Patel, Michael A Rudnicki, Marie-Christine Chaboissier, Anne-Amandine Chassot, Fabien Le Grand
Wnt-mediated signals are involved in many important steps in mammalian regeneration. In multiple cell types, the R-spondin (Rspo) family of secreted proteins potently activates the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. First, we show that deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We find that muscle progenitor cells lacking Rspo1 show delayed differentiation due to reduced activation of Wnt/β-catenin target genes...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28271323/simultaneous-interference-with-her1-egfr-and-rac1-signaling-drives-cytostasis-and-suppression-of-survivin-in-human-glioma-cells-in-vitro
#20
G Karpel-Massler, M-A Westhoff, R E Kast, A Dwucet, S Karpel-Massler, L Nonnenmacher, M D Siegelin, C R Wirtz, K-M Debatin, M-E Halatsch
We have previously reported that combined inhibition of the epidermal growth factor receptor by erlotinib and of RAC1 by NSC23766 yielded a synergistic antiproliferative effect on established and primary cultured glioblastoma cells. The current study aimed at identifying the molecular mechanism. Staining for annexin V/PI or carboxyfluorescein succinimidyl ester was performed in order to determine the induction of apoptosis, necrosis or cytostasis in established and primary cultured glioblastoma cells. Moreover, expression of Ki-67 was determined by immunofluorescence, and the expression of cell cycle proteins was analysed by Western blot...
March 7, 2017: Neurochemical Research
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