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Rac1 RhoA

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https://www.readbyqxmd.com/read/28109909/erk2-zeb1-mir-101-1-axis-contributes-to-epithelial-mesenchymal-transition-and-cell-migration-in-cancer
#1
Kailash Chandra Mangalhara, Siddharth Manvati, Sunil Kumar Saini, Kalaiarasan Ponnusamy, Gaurav Agarwal, Suresh K Abraham, Rameshwar N K Bamezai
Regulation of metastasis continues to remain enigmatic despite our improved understanding of cancer. Identification of microRNAs associated with metastasis in the recent past has provided a new hope. Here, we show how microRNA-101 (miR-101) regulates two independent processes of cellular metastasis by targeting pro-metastatic upstream regulatory transcription factors, ZEB1 and ZEB2, and downstream effector-actin modulators, RHOA and RAC1, providing a single target for therapeutic intervention. Further, we depict how down-regulation of miR-101 by extracellular signal-regulated kinase-2 (ERK2) is vital for MAP kinase pathway induced cellular migration and mesenchymal transition...
January 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28068967/enterolactone-alters-fak-src-signaling-and-suppresses-migration-and-invasion-of-lung-cancer-cell-lines
#2
Shireen Chikara, Kaitlin Lindsey, Pawel Borowicz, Melpo Christofidou-Solomidou, Katie M Reindl
BACKGROUND: Systemic toxicity of chemotherapeutic agents and the challenges associated with targeting metastatic tumors are limiting factors for current lung cancer therapeutic approaches. To address these issues, plant-derived bioactive components have been investigated for their anti-cancer properties because many of these agents are non-toxic to healthy tissues. Enterolactone (EL) is a flaxseed-derived mammalian lignan that has demonstrated anti-migratory properties for various cancers, but EL has not been investigated in the context of lung cancer, and its anticancer mechanisms are ill-defined...
January 9, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27991930/rho-gtpases-anti-or-pro-neoplastic-targets
#3
REVIEW
I Zandvakili, Y Lin, J C Morris, Y Zheng
Rho GTPases are critical signal transducers of multiple pathways. They have been proposed to be useful anti-neoplastic targets for over two decades, especially in Ras-driven cancers. Until recently, however, few in vivo studies had been carried out to test this premise. Several recent mouse model studies have verified that Rac1, RhoA, and some of their effector proteins such as PAK and ROCK, are likely anti-cancer targets for treating K-Ras-driven tumours. Other seemingly contradictory studies have suggested that at least in certain instances inhibition of individual Rho GTPases may paradoxically result in pro-neoplastic effects...
December 19, 2016: Oncogene
https://www.readbyqxmd.com/read/27986909/sos1-arhgef1-and-dock2-rho-gefs-mediate-jak-dependent-lfa-1-activation-by-chemokines
#4
Lara Toffali, Alessio Montresor, Michela Mirenda, Giorgio Scita, Carlo Laudanna
JAK-dependent activation of the rho module of integrin affinity triggering mediates chemokine-induced leukocyte adhesion. However, the signaling events linking JAKs to rho small GTPase activation by chemokines is still incompletely described. In this study, we show that son of sevenless 1 (SOS1), rho guanine nucleotide exchange factor (GEF)1 (ARHGEF1), and dedicator of cytokinesis (DOCK)2 GEFs mediate CXCL12-induced LFA-1 activation in human primary T lymphocytes. Downregulated expression of SOS1, ARHGEF1, and DOCK2 impairs LFA-1-mediated rapid T lymphocyte adhesion as well as underflow arrest on ICAM-1 induced by CXCL12...
December 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27986811/thyroid-cancer-ephb3-stimulates-cell-migration-and-metastasis-in-a-kinase-dependent-manner-through-vav2-rho-gtpase-axis
#5
Jing-Jing Li, Zhi-Jian Sun, Yan-Mei Yuan, Fen-Fen Yin, Yao-Gang Bian, Ling-Yun Long, Xue-Li Zhang, Dong Xie
Eph receptors, the largest subfamily of transmembrane tyrosine kinase receptors, have been increasingly implicated in various physiologic and pathologic processes, and the roles of the Eph family members during tumorigenesis have recently attracted growing attentions. In the present study, we explored the function of EphB3, one member of Eph family, in papillary thyroid cancer (PTC). We found that the expression of EphB3 was significantly elevated in PTC. Either overexpression of EphB3 or activation of EphB3 by EfnB1-Fc/EfnB2-Fc stimulated in vitro migration of PTC cells...
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27927130/p311-accelerates-skin-wound-reepithelialization-by-promoting-epidermal-stem-cell-migration-through-rhoa-and-rac1-activation
#6
Zhihui Yao, Haisheng Li, Weifeng He, Sisi Yang, Xiaorong Zhang, Rixing Zhan, Rui Xu, Jianglin Tan, Junyi Zhou, Jun Wu, Gaoxing Luo
P311 is a newly discovered functional gene, and it has been proved to play a key role in blood pressure homeostasis, glioblastoma invasion, renal fibrosis, hypertrophic scar formation, and others. In this study, for the first time, we found that P311 could enhance reepithelialization during wound healing via promoting epidermal stem cell (EpSC) migration through Rho GTPases. P311 expression was highly increased in neo-epidermal cells during human and mouse skin wound healing, and P311was co-localized with 5-bromo-2'-deoxyuridine positive label-retaining cells in a mouse superficial second-degree burn wound model...
January 3, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/27913679/modelling-gtpase-dynamics-to-understand-rhoa-driven-cancer-cell-invasion
#7
REVIEW
Joseph H R Hetmanski, Jean-Marc Schwartz, Patrick T Caswell
Metastasis, initially driven by cells migrating and invading through the local environment, leads to most cancer-associated deaths. Cells can use a variety of modes to move in vitro, all of which depend on Rho GTPases at some level. While traditionally it was thought that Rac1 activity drives protrusive lamellipodia at the leading edge of a polarised cell while RhoA drives rear retraction, more recent work in 3D microenvironments has revealed a much more complicated picture of GTPase dynamics. In particular, RhoA activity can dominate the leading edge polymerisation of actin to form filopodial actin-spike protrusions that drive more invasive cell migration...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27892530/fine-tuning-of-rac1-and-rhoa-alters-cuspal-shapes-by-remolding-the-cellular-geometry
#8
Liwen Li, Qinghuang Tang, Takashi Nakamura, Jun-Gyo Suh, Hayato Ohshima, Han-Sung Jung
The anatomic and functional combinations of cusps and lophs (ridges) define the tooth shape of rodent molars, which distinguishes species. The species-specific cusp patterns result from the spatiotemporal induction of enamel knots (EKs), which require precisely controlled cellular behavior to control the epithelial invagination. Despite the well-defined roles of EK in cusp patterning, the determinants of the ultimate cuspal shapes and involvement of epithelial cellular geometry are unknown. Using two typical tooth patterns, the lophodont in gerbils and the bunodont in mice, we showed that the cuspal shape is determined by the dental epithelium at the cap stage, whereas the cellular geometry in the inner dental epithelium (IDE) is correlated with the cuspal shape...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852748/quantitative-gtpase-affinity-purification-identifies-rho-family-protein-interaction-partners
#9
Florian Paul, Henrik Zauber, Laura von Berg, Oliver Rocks, Oliver Daumke, Matthias Selbach
Although Rho GTPases are essential molecular switches involved in many cellular processes, an unbiased experimental comparison of their interaction partners was not yet performed. Here, we develop quantitative GTPase affinity purification (qGAP) to systematically identify interaction partners of six Rho GTPases (Cdc42, Rac1, RhoA, RhoB, RhoC, and RhoD), depending on their nucleotide loading state. The method works with cell line or tissue-derived protein lysates in combination with SILAC-based or label-free quantification, respectively...
January 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27849309/activation-of-rac1-and-rhoa-preserve-corneal-endothelial-barrier-function
#10
María C Ortega, Diana Santander-García, Beatriz Marcos-Ramiro, Susana Barroso, Susan Cox, Ignacio Jiménez-Alfaro, Jaime Millán
Purpose: The corneal endothelium is responsible for the correct hydration of the corneal stroma. Corneal endothelial cells have a low proliferative capacity, so preserving their barrier function under suboptimal conditions that cause osmotic imbalance, such as those arising from corneal pathologies, age, cryopreservation, and transplantation, is essential for maintaining corneal transparency. We have investigated the signaling induced by hyperosmotic shock that reversibly disrupts corneal endothelial barriers in human endothelial cells and in murine corneas...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27827394/mitochondrial-ca-2-uptake-controls-actin-cytoskeleton-dynamics-during-cell-migration
#11
Julien Prudent, Nikolay Popgeorgiev, Rudy Gadet, Mathieu Deygas, Ruth Rimokh, Germain Gillet
Intracellular Ca(2+) signaling regulates cell migration by acting on cytoskeleton architecture, cell directionality and focal adhesions dynamics. In migrating cells, cytosolic Ca(2+) pool and Ca(2+) pulses are described as key components of these effects. Whereas the role of the mitochondrial calcium homeostasis and the Mitochondria Cacium Uniporter (MCU) in cell migration were recently highlighted in vivo using the zebrafish model, their implication in actin cystokeleton dynamics and cell migration in mammals is not totally characterized...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27821782/rac1-rhoa-antagonism-defines-cell-to-cell-heterogeneity-during-epidermal-morphogenesis-in-nematodes
#12
Emmanuel Martin, Marie-Hélène Ouellette, Sarah Jenna
The antagonism between the GTPases Rac1 and RhoA controls cell-to-cell heterogeneity in isogenic populations of cells in vitro and epithelial morphogenesis in vivo Its involvement in the regulation of cell-to-cell heterogeneity during epidermal morphogenesis has, however, never been addressed. We used a quantitative cell imaging approach to characterize epidermal morphogenesis at a single-cell level during early elongation of Caenorhabditis elegans embryos. This study reveals that a Rac1-like pathway, involving the Rac/Cdc42 guanine-exchange factor β-PIX/PIX-1 and effector PAK1/PAK-1, and a RhoA-like pathway, involving ROCK/LET-502, control the remodeling of apical junctions and the formation of basolateral protrusions in distinct subsets of hypodermal cells...
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27798233/cd44-a-novel-synaptic-cell-adhesion-molecule-regulating-structural-and-functional-plasticity-of-dendritic-spines
#13
Matylda Roszkowska, Anna Skupien, Tomasz Wójtowicz, Anna Konopka, Adam Gorlewicz, Magdalena Kisiel, Marek Bekisz, Blazej Ruszczycki, Hubert Dolezyczek, Emilia Rejmak, Ewelina Knapska, Jerzy W Mozrzymas, Jakub Wlodarczyk, Grzegorz M Wilczynski, Joanna Dzwonek
Synaptic cell adhesion molecules regulate signal transduction, synaptic function, and plasticity. However, their role in neuronal interactions with the extracellular matrix (ECM) is not well understood. Here we report that the CD44, a transmembrane receptor for hyaluronan, modulates synaptic plasticity. High-resolution ultrastructural analysis showed that CD44 was localized at mature synapses in the adult brain. The reduced expression of CD44 affected the synaptic excitatory transmission of primary hippocampal neurons, simultaneously modifying dendritic spine shape...
December 15, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27795403/the-andes-virus-nucleocapsid-protein-directs-basal-endothelial-cell-permeability-by-activating-rhoa
#14
Elena E Gorbunova, Matthew J Simons, Irina N Gavrilovskaya, Erich R Mackow
: Andes virus (ANDV) predominantly infects microvascular endothelial cells (MECs) and nonlytically causes an acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). In HPS patients, virtually every pulmonary MEC is infected, MECs are enlarged, and infection results in vascular leakage and highly lethal pulmonary edema. We observed that MECs infected with the ANDV hantavirus or expressing the ANDV nucleocapsid (N) protein showed increased size and permeability by activating the Rheb and RhoA GTPases...
October 25, 2016: MBio
https://www.readbyqxmd.com/read/27770633/polymer-fiber-based-models-of-connective-tissue-repair-and-healing
#15
Nancy M Lee, Cevat Erisken, Thomas Iskratsch, Michael Sheetz, William N Levine, Helen H Lu
Physiologically relevant models of wound healing are essential for understanding the biology of connective tissue repair and healing. They can also be used to identify key cellular processes and matrix characteristics critical for the design of soft tissue grafts. Modeling the various stages of repair post tendon injury, polymer meshes of varying fiber diameter (nano-1 (390 nm) < nano-2 (740 nm) < micro (1420 nm)) were produced. Alignment was also introduced in the nano-2 group to model matrix undergoing biological healing rather than scar formation...
January 2017: Biomaterials
https://www.readbyqxmd.com/read/27768516/rho-gtpases-in-mammalian-spinal-neural-tube-closure
#16
Ana Rolo, Sarah Escuin, Nicholas D E Greene, Andrew J Copp
Neural tube closure is an important morphogenetic event that involves dramatic reshaping of both neural and non-neural tissues. Rho GTPases are key cytoskeletal regulators involved in cell motility and in several developmental processes, and are thus expected to play pivotal roles in neurulation. Here, we discuss 2 recent studies that shed light on the roles of distinct Rho GTPases in different tissues during neurulation. RhoA plays an essential role in regulating actomyosin dynamics in the neural epithelium of the elevating neural folds, while Rac1 is required for the formation of cell protrusions in the non-neural surface ectoderm during neural fold fusion...
October 21, 2016: Small GTPases
https://www.readbyqxmd.com/read/27761803/the-pivotal-role-of-ccn2-in-mammalian-palatogenesis
#17
Joseph T Tarr, Timothy G Visser, Joanne E Moon, Honey Hendesi, Mary F Barbe, James P Bradley, Steven N Popoff
Mammalian palatogenesis is a complex process involving a temporally and spatially regulated myriad of factors. Together these factors control the 3 vital processes of proliferation, elevation and fusion of the developing palate. In this study, we show for the first time the unequivocally vital role of CCN2 in development of the mammalian palate. We utilized CCN2 knockout (KO) mice and cranial neural crest derived mesenchymal cells from these CCN2 KO mice to investigate the 3 processes crucial to normal palatogenesis...
October 20, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27754741/arf6-and-its-zeb1-epb41l5-mesenchymal-axis-are-required-for-both-mesenchymal-and-amoeboid-type-invasion-of-cancer-cells
#18
Haruka Handa, Ari Hashimoto, Shigeru Hashimoto, Hisataka Sabe
Modes of cancer invasion interchange between the mesenchymal type and amoeboid type in response to the microenvironment, in which RhoA and Rac1 are selectively required to perform different modes of actin-cytoskeletal remodeling. Membrane remodeling is another integral part of invasion. Arf6 regulates the recycling of molecules at the cell periphery, and is often overexpressed in malignant cancers together with its effector AMAP1/ASAP1/DDEF1. This pathway promotes mesenchymal-type invasion when AMAP1 binds to EPB41L5, a mesenchymal-specific protein induced by ZEB1...
October 18, 2016: Small GTPases
https://www.readbyqxmd.com/read/27729281/ganglioside-gm3-mediates-glucose-induced-suppression-of-igf-1-receptor-rac1-activation-to-inhibit-keratinocyte-motility
#19
Duncan Hieu M Dam, Xiao-Qi Wang, Sarah Sheu, Mahima Vijay, Desmond Shipp, Luke Miller, Amy S Paller
Activation of insulin-like growth factor-1 (IGF-1) receptor (IGF1R) signaling induces keratinocyte migration, but little is known about its regulation, including in diabetic wounds. GM3, a lipid raft ganglioside synthesized by GM3 synthase (GM3S), regulates receptor signaling. In diabetic mice, knockout or topically applied nanoconstruct-mediated knockdown of GM3S promotes wound edge IGF1R phosphorylation and re-epithelialization. Through modulating GM3 expression, we explored the role of GM3 in regulating human keratinocyte IGF1R signaling...
October 8, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27726098/downregulation-of-arhgdia-contributes-to-human-glioma-progression-through-activation-of-rho-gtpase-signaling-pathway
#20
Weiliang Lu, Xixi Wang, Jingjing Liu, Yu He, Ziwei Liang, Zijing Xia, Ying Cai, Liangxue Zhou, Hongxia Zhu, Shufang Liang
The protein ARHGDIA has been found to play distinct roles in cancer progression for several tumors. However, it remains elusive whether and how ARHGDIA plays functions in human glioma. In this study, we discovered that ARHGDIA is much downregulated in human glioma; meanwhile, its expression negatively correlates with glioma malignancy and positively relates to prognosis of glioma patients. It has independent predictive value of ARHGDIA expression level for overall survival of human glioma patients. Glioma patients with ARHGDIA-positive expression have a longer overall survival time than ARHGDIA-negative patients...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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