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https://www.readbyqxmd.com/read/27930970/astragaloside-iv-inhibits-breast-cancer-cell-invasion-by-suppressing-vav3-mediated-rac1-mapk-signaling
#1
Ke Jiang, Qing Lu, Qiong Li, Yajie Ji, Weili Chen, Xiaohong Xue
BACKGROUND: Astragaloside IV (AS-IV), the major active triterpenoid in Radix Astragali, has shown anti-tumorigenic properties in certain cancers; however, its role in breast cancer remains unclear. The present study investigated the effects of AS-IV on breast cancer in vitro and in vivo and examined the underlying mechanisms. METHODS: The effects of AS-IV on MDA-MB-231 cell proliferation, migration, invasion and metastasis were investigated by MTT and Transwell assays, and western blotting...
December 5, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27927130/p311-accelerates-skin-wound-reepithelialization-by-promoting-epidermal-stem-cell-migration-through-rho-a-and-rac1-activation
#2
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, which has been proven to play a key role in blood pressure homeostasis, glioblastoma invasion, renal fibrosis, hypertrophic scar formation and others. In this study, we for the first time 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 BrdU positive label-retaining cells in a mouse superficial second degree burn wound model...
December 8, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27922761/%C3%AE-6%C3%AE-4-integrin-regulates-the-collective-migration-of-epithelial-cells
#3
Zachary T Colburn, Jonathan C R Jones
α6β4 integrin is localized in a unique punctate distribution at the cell-substratum interface along the leading front of single, front-rear polarized, A549 cells. These puncta are interspersed between focal adhesions and lack association with the actin cytoskeleton. Knockdown of β4 integrin in A549 cells inhibits their directed migration, with knockdown cells exhibiting large focal adhesions and reduced actin dynamics. Despite these changes, the speed of knockdown cells is equivalent to controls cells. Interestingly, in such cells, α6 integrin retains its punctate distribution...
December 6, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27920252/group-i-paks-promote-skeletal-myoblast-differentiation-in-vivo-and-in-vitro
#4
Giselle A Joseph, Min Lu, Maria Radu, Jennifer K Lee, Steven J Burden, Jonathan Chernoff, Robert S Krauss
Skeletal myogenesis is regulated by signal transduction, but the factors and mechanisms involved are not well understood. The group I Paks, Pak1 and Pak2, are related protein kinases and direct effectors of Cdc42 and Rac1. Group I Paks are ubiquitously expressed and specifically required for myoblast fusion in Drosophila We report that both Pak1 and Pak2 are activated during mammalian myoblast differentiation. One pathway of activation is initiated by N-cadherin ligation, and involves the cadherin co-receptor Cdo with its downstream effector, Cdc42...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27913679/modelling-gtpase-dynamics-to-understand-rhoa-driven-cancer-cell-invasion
#5
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/27912197/rac1-nadph-oxidase-signaling-promotes-cd36-activation-under-glucotoxic-conditions-in-pancreatic-beta-cells
#6
Suma Elumalai, Udayakumar Karunakaran, In Kyu Lee, Jun Sung Moon, Kyu Chang Won
We recently reported that cluster determinant 36 (CD36), a fatty acid transporter, plays a pivotal role in glucotoxicity-induced β-cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression. Emerging evidence suggests that the small GTPase Rac1 is involved in the pathogenesis of beta cell dysfunction in type 2 diabetes (T2D). The primary objective of the current study was to determine the role of Rac1 in CD36 activation and its impact on β-cell dysfunction in diabetes mellitus...
November 23, 2016: Redox Biology
https://www.readbyqxmd.com/read/27908735/unr-csde1-drives-a-post-transcriptional-program-to-promote-melanoma-invasion-and-metastasis
#7
Laurence Wurth, Panagiotis Papasaikas, David Olmeda, Nadine Bley, Guadalupe T Calvo, Santiago Guerrero, Daniela Cerezo-Wallis, Javier Martinez-Useros, María García-Fernández, Stefan Hüttelmaier, Maria S Soengas, Fátima Gebauer
RNA binding proteins (RBPs) modulate cancer progression through poorly understood mechanisms. Here we show that the RBP UNR/CSDE1 is overexpressed in melanoma tumors and promotes invasion and metastasis. iCLIP sequencing, RNA sequencing, and ribosome profiling combined with in silico studies unveiled sets of pro-metastatic factors coordinately regulated by UNR as part of RNA regulons. In addition to RNA steady-state levels, UNR was found to control many of its targets at the level of translation elongation/termination...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27904138/cirmtuzumab-inhibits-wnt5a-induced-rac1-activation-in-chronic-lymphocytic-leukemia-treated-with-ibrutinib
#8
J Yu, L Chen, B Cui, C Wu, M Y Choi, Y Chen, L Zhang, L Z Rassenti, G F Widhopf, T J Kipps
Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival...
December 1, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27904039/role-of-rac1-wave2-signaling-in-mediating-the-inhibitory-effects-of-%C3%AE-tocotrienol-on-mammary-cancer-cell-migration-and-invasion
#9
Ibrahim Gayadh Algayadh, Venkateshwararao Dronamraju, Paul William Sylvester
The majority of breast cancer deaths result from the progression of this disease to a metastatic phenotype. Rac1 and Cdc42 are Rho family members that together with their downstream effectors, Wiskott-Aldrich Syndrome protein-family verprolin-homologous protein 2 (WAVE2) and Arp2/3, play an important role in cytoskeletal reorganization and the formation of membrane protrusions that promote cancer cell migration and invasion. γ-Tocotrienol, is a natural isoform within the vitamin E family of compounds that inhibits breast cancer cell growth and progression by suppressing various signaling pathways involved in mitogenic signaling and metastatic progression...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27902969/rac1-gtp-ase-signals-wnt-beta-catenin-pathway-mediated-integrin-directed-metastasis-associated-tumor-cell-phenotypes-in-triple-negative-breast-cancers
#10
Pradip De, Jennifer H Carlson, Tyler Jepperson, Scooter Willis, Brian Leyland-Jones, Nandini Dey
The acquisition of integrin-directed metastasis-associated (ID-MA) phenotypes by Triple-Negative Breast Cancer (TNBC) cells is caused by an upregulation of the Wnt-beta-catenin pathway (WP). We reported that WP is one of the salient genetic features of TNBC. RAC-GTPases, small G-proteins which transduce signals from cell surface proteins including integrins, have been implicated in tumorigenesis and metastasis by their role in essential cellular functions like motility. The collective percentage of alteration(s) in RAC1 in ER+ve BC was lower as compared to ER-ve BC (35% vs 57%) (brca/tcga/pub2015)...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27892530/fine-tuning-of-rac1-and-rhoa-alters-cuspal-shapes-by-remolding-the-cellular-geometry
#11
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/27891552/enteric-glial-cells-are-susceptible-to-clostridium-difficile-toxin-b
#12
Katia Fettucciari, Pamela Ponsini, Davide Gioè, Lara Macchioni, Camilla Palumbo, Elisabetta Antonelli, Stefano Coaccioli, Vincenzo Villanacci, Lanfranco Corazzi, Pierfrancesco Marconi, Gabrio Bassotti
Clostridium difficile causes nosocomial/antibiotic-associated diarrhoea and pseudomembranous colitis. The major virulence factors are toxin A and toxin B (TcdB), which inactivate GTPases by monoglucosylation, leading to cytopathic (cytoskeleton alteration, cell rounding) and cytotoxic effects (cell-cycle arrest, apoptosis). C. difficile toxins breaching the intestinal epithelial barrier can act on underlying cells, enterocytes, colonocytes, and enteric neurons, as described in vitro and in vivo, but until now no data have been available on enteric glial cell (EGC) susceptibility...
November 28, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27890785/genomic-characterization-of-dysplastic-nevi-unveils-implications-for-diagnosis-of-melanoma
#13
Rachel D Melamed, Iraz T Aydin, Geena Susan Rajan, Robert Phelps, David N Silvers, Kevin J Emmett, Georg Brunner, Raul Rabadan, Julide Tok Celebi
A well-defined risk factor and precursor for cutaneous melanoma is the dysplastic nevus. These benign tumors represent clonal hyperproliferation of melanocytes that are in a senescent-like state, but with occasional malignant transformation events. To portray the mutational repertoire of dysplastic nevi in patients with the dysplastic nevus syndrome, and to determine the discriminatory profiles of melanocytic nevi (including dysplastic nevi) from melanoma, we sequenced exomes of melanocytic nevi including dysplastic nevi (n = 19), followed by a targeted gene panel (785 genes) characterization of melanocytic nevi (n = 46) and primary melanomas (n = 42)...
November 24, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27890541/the-expression-of-plasticity-related-genes-in-an-acute-model-of-stress-is-modulated-by-chronic-desipramine-in-a-time-dependent-manner-within-medial-prefrontal-cortex
#14
Nicoletta Nava, Giulia Treccani, Heidi Kaastrup Müller, Maurizio Popoli, Gregers Wegener, Betina Elfving
It is well established that stress plays a major role in the pathogenesis of neuropsychiatric diseases. Stress-induced alteration of synaptic plasticity has been hypothesized to underlie the morphological changes observed by neuroimaging in psychiatric patients in key regions such as hippocampus and prefrontal cortex (PFC). We have recently shown that a single acute stress exposure produces significant short-term alterations of structural plasticity within medial PFC. These alterations were partially prevented by previous treatment with chronic desipramine (DMI)...
November 24, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27888097/rab7a-regulates-cell-migration-through-rac1-and-vimentin
#15
Azzurra Margiotta, Cinzia Progida, Oddmund Bakke, Cecilia Bucci
Rab7a, a small GTPase of the Rab family, is localized to late endosomes and controls late endocytic trafficking. The discovery of several Rab7a interacting proteins revealed that Rab7a function is closely connected to cytoskeletal elements. Indeed, Rab7a recruits on vesicles RILP and FYCO that are responsible for the movement of Rab7a-positive vesicles and/or organelles on microtubule tracks, but also directly interacts with Rac1, a fundamental regulator of actin cytoskeleton, and with peripherin and vimentin, two intermediate filament proteins...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27886395/popdc1-bves-functions-in-the-preservation-of-cardiomyocyte-viability-while-affecting-rac1-activity-and-bnip3-expression
#16
Kliminski Vitaly, Uziel Orit, Kessler-Icekson Gania
The Popeye domain containing1, also called Bves (Popdc1/Bves), is a transmembrane protein that functions in muscle regeneration, heart rate regulation, hypoxia tolerance, and ischemia preconditioning. The expression of Popdc1/Bves is elevated in cardiomyocytes maintained in serum free defined medium. We hypothesized that Popdc1/Bves is important for cardiomyocyte survival under the stress of serum deprivation and investigated the mechanisms involved. A deficit in Popdc1/Bves, achieved by siRNA-mediated gene silencing, results in cardiomyocyte injury and death, upregulation of the pro-apoptotic protein Bcl-2/adenovirus E1B 19-kDa interacting protein3 (Bnip3), as well as reduction in Rac1-GTPase activity and in Akt phosphorylation...
November 25, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27886249/impairment-of-pdgf-induced-chemotaxis-by-extracellular-%C3%AE-synuclein-through-selective-inhibition-of-rac1-activation
#17
Taro Okada, Chihoko Hirai, Shaymaa Mohamed Mohamed Badawy, Lifang Zhang, Taketoshi Kajimoto, Shun-Ichi Nakamura
Parkinson's disease (PD) is characterized by α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies. Although it is known that extracellular α-Syn is detected in the plasma and cerebrospinal fluid, its physiological significance remains unclear. Here, we show that extracellular α-Syn suppresses platelet-derived growth factor (PDGF)-induced chemotaxis in human neuroblastoma SH-SY5Y cells. The inhibitory effect was stronger in the mutant α-Syn(A53T), found in hereditary PD, and the degree of inhibition was time-dependent, presumably because of the oligomerization of α-Syn...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881869/netrin-1-induced-stem-cell-bioactivity-contributes-to-the-regeneration-of-injured-tissues-via-the-lipid-raft-dependent-integrin-%C3%AE-6%C3%AE-4-signaling-pathway
#18
Soo Sang Lee, Sei-Jung Lee, Sang Hun Lee, Jung Min Ryu, Hyeon Su Lim, Jun Sung Kim, Eun Ju Song, Young Hyun Jung, Hyun Jik Lee, Chung Hun Kim, Ho Jae Han
Netrin-1 (Ntn-1) is a multifunctional neuronal signaling molecule; however, its physiological significance, which improves the tissue-regeneration capacity of stem cells, has not been characterized. In the present study, we investigate the mechanism by which Ntn-1 promotes the proliferation of hUCB-MSCs with regard to the regeneration of injured tissues. We found that Ntn-1 induces the proliferation of hUCB-MSCs mainly via Inα6β4 coupled with c-Src. Ntn-1 induced the recruitment of NADPH oxidases and Rac1 into membrane lipid rafts to facilitate ROS production...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881661/par3-integrates-tiam1-and-phosphatidylinositol-3-kinase-signaling-to-change-apical-membrane-identity
#19
Travis R Ruch, David M Bryant, Keith E Mostov, Joanne N Engel
Pathogens can alter epithelial polarity by recruiting polarity proteins to the apical membrane, but how a change in protein localization is linked to polarity disruption is not clear. In this study we used chemically induced dimerization to rapidly relocalize proteins from the cytosol to the apical surface. We demonstrate that forced apical localization of Par3, which is normally restricted to tight junctions, is sufficient to alter apical membrane identity through its interactions with phosphatidylinositol 3-Kinase (PI3K) and the Rac1 guanine nucleotide exchange factor Tiam1...
November 23, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27877226/rac1-overexpression-is-correlated-with-epithelial-mesenchymal-transition-and-predicts-poor-prognosis-in-non-small-cell-lung-cancer
#20
Yujuan Zhou, Qianjin Liao, Yaqian Han, Jie Chen, Zhigang Liu, Hang Ling, Jing Zhang, Wenjuan Yang, Linda Oyang, Longzheng Xia, Li Wang, Heran Wang, Lei Xue, Hui Wang, Bingqiang Hu
Objective: Ras-related C3 botulinum toxin substrate1(Rac1) and epithelial mesenchymal transition (EMT) are key therapeutic targets in cancer. We investigated the clinical significance of Rac1 and markers of EMT expression in non-small cell lung cancer (NSCLC), and their possible correlation with EMT phenotype. Methods: Immunohistochemistry was used to assess the expression of Rac1, Snail1, Twist1, N-cadherin (N-cad), Vimentin (Vim), and E-cadherin (E-cad) in 153 NSCLC paraffin-embedded specimens and 45 normal specimens adjacent to tumors...
2016: Journal of Cancer
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