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Rac1 RhoA

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https://www.readbyqxmd.com/read/29454618/natural-small-molecule-bigelovin-suppresses-orthotopic-colorectal-tumor-growth-and-inhibits-colorectal-cancer-metastasis-via-il6-stat3-pathway
#1
Mingyue Li, Grace Gar-Lee Yue, Li-Hua Song, Mao-Bo Huang, Julia Kin-Ming Lee, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Ning-Hua Tan, Clara Bik-San Lau
Bigelovin, a sesquiterpene lactone, has been demonstrated to induce apoptosis, inhibit inflammation and angiogenesis in vitro, but its potential anti-metastatic activity remains unclear. In the present study, two colon cancer mouse models, orthotopic tumor allografts and experimental metastatic models were utilized to investigate the progression and metastatic spread of colorectal cancer after bigelovin treatments. Results showed that bigelovin (intravenous injection; 0.3-3 mg/kg) significantly suppressed tumor growth and inhibited liver/lung metastasis with modulation of tumor microenvironment (e...
February 15, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29440144/spon2-promotes-m1-like-macrophage-recruitment-and-inhibits-hepatocellular-carcinoma-metastasis-by-distinct-integrin-rho-gtpase-hippo-pathways
#2
Yan-Li Zhang, Qing Li, Xiao-Mei Yang, Fang Fang, Jun Li, Ya-Hui Wang, Qin Yang, Lei Zhu, Hui-Zhen Nie, Xue-Li Zhang, Ming-Xuan Feng, Shu-Heng Jiang, Guang-Ang Tian, Li-Peng Hu, Ho-Young Lee, Su-Jae Lee, Qiang Xia, Zhi-Gang Zhang
Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis...
February 13, 2018: Cancer Research
https://www.readbyqxmd.com/read/29432898/acarbose-inhibits-the-proliferation-and-migration-of-vascular-smooth-muscle-cells-via-targeting-ras-signaling
#3
Meng-Hsun Yu, Ming-Cheng Lin, Chien-Ning Huang, Kuei-Chuan Chan, Chau-Jong Wang
Atherosclerosis involves the proliferation and migration of vascular smooth muscle cells (VSMCs). The migration of VSMCs from the media into the intima and their subsequent proliferation are important processes in neointima formation in atherosclerosis and restenosis after percutaneous coronary interventions. Acarbose, an alpha-glucosidase inhibitor, has been demonstrated to not affect serum levels of glucose and decrease the progression of intima-media thickening in rabbits fed with a high cholesterol diet (HCD)...
February 9, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29424004/substrate-stiffness-regulated-migration-and-invasion-ability-of-adenoid-cystic-carcinoma-cells-via-rhoa-rock-pathway
#4
Dan Zhao, Qianshun Li, Mengting Liu, Wenjuan Ma, Tengfei Zhou, Changyue Xue, Xiaoxiao Cai
OBJECTIVES: Human salivary adenoid cystic carcinoma (SACC) is one of the most common malignant tumours of the salivary gland and has strong migratory and invasive ability, which often lead to poor prognosis and lower survival rate. Tumour tissue tends to stiffen during solid tumour progression. This study aimed to investigate the influence of various substrate stiffness on the migration and invasion of SACC. METHODS: Salivary adenoid cystic carcinoma cell line ACC2 cells were cultured on polydimethylsiloxane substrates (PDMS) with varying stiffness for investigating the effects of substrate stiffness on the activities of MMPs and TIMPs...
February 8, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29406266/systemic-or-forebrain-neuron-specific-deficiency-of-geranylgeranyltransferase-1-impairs-synaptic-plasticity-and-reduces-dendritic-spine-density
#5
David Hottman, Shaowu Cheng, Andrea Gram, Kyle LeBlanc, Li-Lian Yuan, Ling Li
Isoprenoids and prenylated proteins regulate a variety of cellular functions, including neurite growth and synaptic plasticity. Importantly, they are implicated in the pathogenesis of several diseases, including Alzheimer's disease (AD). Recently, we have shown that two protein prenyltransferases, farnesyltransferase (FT) and geranylgeranyltransferase-1 (GGT), have differential effects in a mouse model of AD. Haplodeficiency of either FT or GGT attenuates amyloid-β deposition and neuroinflammation but only reduction in FT rescues cognitive function...
February 2, 2018: Neuroscience
https://www.readbyqxmd.com/read/29377591/carboxylated-graphene-oxide-promoted-axonal-guidance-growth-by-activating-netrin-1-dcc-signaling-in-rat-primary-cultured-cortical-neurons
#6
Meili Liu, Zhengtai Jia, Xiongfu Xiao, Zhifa Zhang, Ping Li, Gang Zhou, Yubo Fan
Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the neuronal guidance growth are still not reported. In the present study, graphene oxide (GO) and Carboxylated graphene oxide (GO-COOH) were used to investigate the potential effects on axonal guidance growth in the primary cultured cortical neurons. In addition,we characterized the structure and chemical composition of synthesized graphene oxide (GO) and carboxylated graphene oxide (GO-COOH) using Fourier transform infrared (FT-IR) spectrophotometer and Scanning Electron Microscope (SEM) assays and Raman analysis...
January 29, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29374533/circadian-control-of-p75-neurotrophin-receptor-leads-to-alternate-activation-of-nrf2-and-c-rel-to-reset-energy-metabolism-in-astrocytes-via-brain-derived-neurotrophic-factor
#7
REVIEW
Tetsuro Ishii, Eiji Warabi, Giovanni E Mann
Circadian clock genes regulate energy metabolism partly through neurotrophins in the body. The low affinity neurotrophin receptor p75NTR is a clock component directly regulated by the transcriptional factor Clock:Bmal1 complex. Brain-derived neurotrophic factor (BDNF) is expressed in the brain and plays a key role in coordinating metabolic interactions between neurons and astrocytes. BDNF transduces signals through TrkB and p75NTR receptors. This review highlights a novel molecular mechanism by which BDNF via circadian control of p75NTR leads to daily resetting of glucose and glycogen metabolism in brain astrocytes to accommodate their functional interaction with neurons...
January 24, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29373579/an-akap-lbc-rhoa-interaction-inhibitor-promotes-the-translocation-of-aquaporin-2-to-the-plasma-membrane-of-renal-collecting-duct-principal-cells
#8
Katharina Schrade, Jessica Tröger, Adeeb Eldahshan, Kerstin Zühlke, Kamal R Abdul Azeez, Jonathan M Elkins, Martin Neuenschwander, Andreas Oder, Mohamed Elkewedi, Sarah Jaksch, Karsten Andrae, Jinliang Li, Joao Fernandes, Paul Markus Müller, Stephan Grunwald, Stephen F Marino, Tanja Vukićević, Jenny Eichhorst, Burkhard Wiesner, Marcus Weber, Michael Kapiloff, Oliver Rocks, Oliver Daumke, Thomas Wieland, Stefan Knapp, Jens Peter von Kries, Enno Klussmann
Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown...
2018: PloS One
https://www.readbyqxmd.com/read/29370168/a-switch-in-the-mode-of-wnt-signaling-orchestrates-the-formation-of-germline-stem-cell-differentiation-niche-in-drosophila
#9
Maitreyi Upadhyay, Michael Kuna, Sara Tudor, Yesenia Martino Cortez, Prashanth Rangan
Germline stem cell (GSC) self-renewal and differentiation into gametes is regulated by both intrinsic factors in the germ line as well as extrinsic factors from the surrounding somatic niche. dWnt4, in the escort cells of the adult somatic niche promotes GSC differentiation using the canonical β-catenin-dependent transcriptional pathway to regulate escort cell survival, adhesion to the germ line and downregulation of self-renewal signaling. Here, we show that in addition to the β-catenin-dependent canonical pathway, dWnt4 also uses downstream components of the Wnt non-canonical pathway to promote escort cell function earlier in development...
January 25, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29366821/a-rho-gtpase-based-model-explains-spontaneous-collective-migration-of-neural-crest-cell-clusters
#10
Brian Merchant, Leah Edelstein-Keshet, James J Feng
We propose a model to explain the spontaneous collective migration of neural crest cells in the absence of an external gradient of chemoattractants. The model is based on the dynamical interaction between Rac1 and RhoA that is known to regulate the polarization, contact inhibition and co-attraction of neural crest cells. Coupling the reaction-diffusion equations for active and inactive Rac1 and RhoA on the cell membrane with a mechanical model for the overdamped motion of membrane vertices, we show that co-attraction and contact inhibition cooperate to produce persistence of polarity in a cluster of neural crest cells by suppressing the random onset of Rac1 hotspots that may mature into new protrusion fronts...
January 20, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29363851/wild-type-p53-enhances-endothelial-barrier-function-by-mediating-rac1-signalling-and-rhoa-inhibition
#11
Nektarios Barabutis, Christiana Dimitropoulou, Betsy Gregory, John D Catravas
Inflammation is the major cause of endothelial barrier hyper-permeability, associated with acute lung injury and acute respiratory distress syndrome. This study reports that p53 "orchestrates" the defence of vascular endothelium against LPS, by mediating the opposing actions of Rac1 and RhoA in pulmonary tissues. Human lung microvascular endothelial cells treated with HSP90 inhibitors activated both Rac1- and P21-activated kinase, which is an essential element of vascular barrier function. 17AAG increased the phosphorylation of both LIMK and cofilin, in contrast to LPS which counteracted those effects...
January 24, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29363728/interleukin-17-induces-angiogenesis-in-vitro-via-cxcl8-and-ccl2-in-retinal-pigment-epithelium
#12
Ying Chen, Murui Zhong, Gangxiang Yuan, Hui Peng
Interleukin-17 (IL-17) is a major pro-inflammatory cytokine involved in choroidal endothelial cell (CEC) angiogenesis. Proteins expressed by the retinal pigment epithelium (RPE) may contribute to CEC angiogenesis. The ability of IL‑17 to promote proliferation, migration and capillary‑like structure formation in CECs was investigated by stimulating the RPE in vitro. CECs were cultured in a conditioned medium (CM) with IL‑17 (IL‑17‑CM) or without IL‑17 (CM) obtained from the supernatant of an ARPE‑19 cell line...
March 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29323050/long-non-coding-rna-nonmmug014387-promotes-schwann-cell-proliferation-after-peripheral-nerve-injury
#13
Bin Pan, Zhong-Ju Shi, Jia-Yin Yan, Jia-He Li, Shi-Qing Feng
Schwann cells play a critical role in peripheral nerve regeneration through dedifferentiation and proliferation. In a previous study, we performed microarray analysis of the sciatic nerve after injury. Accordingly, we predicted that long non-coding RNA NONMMUG014387 may promote Schwann cell proliferation after peripheral nerve injury, as bioinformatic analysis revealed that the target gene of NONMMUG014387 was collagen triple helix repeat containing 1 (Cthrc1). Cthrc1 may promote cell proliferation in a variety of cells by activating Wnt/PCP signaling...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29312635/lrp6-promotes-invasion-and-metastasis-of-colorectal-cancer-through-cytoskeleton-dynamics
#14
Qian Yao, Yu An, Wei Hou, Ya-Nan Cao, Meng-Fei Yao, Ning-Ning Ma, Lin Hou, Hong Zhang, Hai-Jing Liu, Bo Zhang
Low density lipoprotein (LDL) receptor-related protein-6 (LRP6) is an important co-receptor of Wnt pathway, which plays a predominant role in development and progression of colorectal cancer. Recently, dysregulation of LRP6 has proved to be involved in the progression of cancers, but its biological role and clinical significance in colorectal cancer remain unclear. In present study, we revealed that phosphorylation of LRP6 was aberrantly upregulated in colorectal carcinoma correlating with TNM or Dukes staging and worse prognosis...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29307615/protein-phosphatase-1b-dephosphorylates-rho-guanine-nucleotide-dissociation-inhibitor-1-and-suppresses-cancer-cell-migration-and-invasion
#15
Hee Jun Cho, Jong-Tae Kim, Seon-Jin Lee, Yo Sep Hwang, Sang Yoon Park, Bo-Yeon Kim, Jiyun Yoo, Kwan Soo Hong, Jeong-Ki Min, Chul-Ho Lee, Jong-Seok Lim, Suk Ran Yoon, Inpyo Choi, Yong-Kyung Choe, Hee Gu Lee
Rho GTPases control a wide range of cellular processes, and their deregulation is associated with promotion of an aggressive and metastatic tumor phenotype in human cancers. Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1) plays a key role in regulating the activity of Rho GTPases. However, the underlying mechanisms are still unclear. In this study, we show that protein phosphatase 1B (PPM1B) interacts with RhoGDI1 and functions as its phosphatase. Ectopic expression of PPM1B results in dephosphorylation of RhoGDI1 and, thereby, abates the activation of RhoA, Rac1 and CDC42 by epidermal growth factor (EGF)...
January 4, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29301608/selective-regulation-of-osteoclast-adhesion-and-spreading-by-plc%C3%AE-pkc%C3%AE-pkc%C3%AE-rhoa-rac1-signaling
#16
Jin-Man Kim, Kyunghee Lee, Daewon Jeong
Bone resorption by multinucleated osteoclasts is a multistep process involving adhesion to the bone matrix, migration to resorption sites, and formation of sealing zones and ruffled borders. Macrophage colony-stimulating factor (M-CSF) and osteopontin (OPN) have been shown to be involved in the bone resorption process by respective activation of integrin αvβ3 via "inside-out" and "outside-in" signaling. In this study, we investigated the link between signal modulators known to M-CSF- and OPN-induced osteoclast adhesion and spreading...
January 5, 2018: BMB Reports
https://www.readbyqxmd.com/read/29279389/rsk2-drives-cell-motility-by-serine-phosphorylation-of-larg-and-activation-of-rho-gtpases
#17
Geng-Xian Shi, Won Seok Yang, Ling Jin, Michelle L Matter, Joe W Ramos
Directed migration is essential for cell motility in many processes, including development and cancer cell invasion. RSKs (p90 ribosomal S6 kinases) have emerged as central regulators of cell migration; however, the mechanisms mediating RSK-dependent motility remain incompletely understood. We have identified a unique signaling mechanism by which RSK2 promotes cell motility through leukemia-associated RhoGEF (LARG)-dependent Rho GTPase activation. RSK2 directly interacts with LARG and nucleotide-bound Rho isoforms, but not Rac1 or Cdc42...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29251710/mesenchymal-stem-cell-derived-extracellular-vesicles-attenuate-pulmonary-vascular-permeability-and-lung-injury-induced-by-hemorrhagic-shock-and-trauma
#18
Daniel R Potter, Byron Y Miyazawa, Stuart L Gibb, Xutao Deng, Padma P Togaratti, Roxanne H Croze, Amit K Srivastava, Alpa Trivedi, Michael Matthay, John B Holcomb, Martin A Schreiber, Shibani Pati
BACKGROUND: Mesenchymal Stem Cells (MSCs) have been shown to mitigate vascular permeability in hemorrhagic shock (HS) and trauma induced brain and lung injury. Mechanistically, paracrine factors secreted from MSCs have been identified that can recapitulate many of the potent biologic effects of MSCs in animal models of disease. Interestingly, MSC derived extracellular vesicles (EVs), contain many of these key soluble factors, and have therapeutic potential independent of the parent cells...
December 14, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/29246246/rho-gtpases-as-therapeutic-targets-in-alzheimer-s-disease
#19
REVIEW
Byron J Aguilar, Yi Zhu, Qun Lu
The progress we have made in understanding Alzheimer's disease (AD) pathogenesis has led to the identification of several novel pathways and potential therapeutic targets. Rho GTPases have been implicated as critical components in AD pathogenesis, but their various functions and interactions make understanding their complex signaling challenging to study. Recent advancements in both the field of AD and Rho GTPase drug development provide novel tools for the elucidation of Rho GTPases as a viable target for AD...
December 15, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29242313/dissection-of-glomerular-transcriptional-profile-in-patients-with-diabetic-nephropathy-srgap2a-protects-podocyte-structure-and-function
#20
Yu Pan, Song Jiang, Qing Hou, Dandan Qiu, Jingsong Shi, Ling Wang, Zhaohong Chen, Mingchao Zhang, Aiping Duan, Weisong Qin, Ke Zen, Zhihong Liu
Podocytes play a pivotal role in maintaining glomerular filtration function through their interdigitated foot processes. However, the mechanisms that govern the podocyte cytoskeletal rearrangement still remain unclear. Through analyzing transcriptional profile of renal biopsy from diabetic nephropathy (DN) patients and control donors, we identify Slit-Robo GTP activating protein 2a (SRGAP2a) as one of the main 'hub' genes that are strongly associated with proteinuria and glomerular filtration in type 2 DN patients...
December 14, 2017: Diabetes
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