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https://www.readbyqxmd.com/read/28634582/cancer-stem-cells-in-moderately-differentiated-lip-squamous-cell-carcinoma-express-components-of-the-renin-angiotensin-system
#1
Rachna S Ram, Helen D Brasch, Jonathan C Dunne, Paul F Davis, Swee T Tan, Tinte Itinteang
AIM: We investigated the expression of the renin-angiotensin system (RAS) by cancer stem cell (CSC) subpopulations we have identified in moderately differentiated lip squamous cell carcinoma (MDLSCC). METHOD: Ten MDLSCC samples underwent 3,3-diaminobenzidine (DAB) and immunofluorescent immunohistochemical (IHC) staining for (pro)renin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1), and receptor 2 (ATIIR2). NanoString analysis and Western blotting (WB) were performed on six MDLSCC samples for gene and protein expression, respectively...
2017: Frontiers in Surgery
https://www.readbyqxmd.com/read/28634262/rassf4-regulator-of-plasma-membrane-pi-4-5-p2
#2
Eamonn J Dickson
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a negatively charged phospholipid that plays a major role in recruiting and regulating proteins at the plasma membrane-cytosol interface. In this issue, Chen et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201606047) demonstrate that RAS association domain family 4 (RASSF4) positively influences PI(4,5)P2 synthesis through ARF6-dependent regulation of PIP5K.
June 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28634209/genetic-evidence-that-%C3%AE-arrestins-are-dispensable-for-the-initiation-of-%C3%AE-2-adrenergic-receptor-signaling-to-erk
#3
Morgan O'Hayre, Kelsie Eichel, Silvia Avino, Xuefeng Zhao, Dana J Steffen, Xiaodong Feng, Kouki Kawakami, Junken Aoki, Karen Messer, Roger Sunahara, Asuka Inoue, Mark von Zastrow, J Silvio Gutkind
The β2-adrenergic receptor (β2AR) has provided a paradigm to elucidate how G protein-coupled receptors (GPCRs) control intracellular signaling, including the discovery that β-arrestins, which bind to ligand-activated GPCRs, are central for GPCR function. We used genome editing, conditional gene deletion, and small interfering RNAs (siRNAs) to determine the roles of β-arrestin 1 (β-arr1) and β-arr2 in β2AR internalization, trafficking, and signaling to ERK. We found that only β-arr2 was essential for β2AR internalization...
June 20, 2017: Science Signaling
https://www.readbyqxmd.com/read/28632027/shc-and-the-mechanotransduction-of-cellular-anchorage-and-metastasis
#4
Lance S Terada
Tissue cells continually monitor anchorage conditions by gauging the physical properties of their underlying matrix and surrounding environment. The Rho and Ras GTPases are essential components of these mechanosensory pathways. These molecular switches control both cytoskeletal as well as cell fate responses to anchorage conditions and are thus critical to our understanding of how cells respond to their physical environment and, by extension, how malignant cells gainsay these regulatory pathways. Recent studies indicate that 2 proteins produced by the SHC1 gene, thought for the most part to functionally oppose each other, collaborate in their ability to respond to mechanical force by initiating respective Rho and Ras signals...
February 17, 2017: Small GTPases
https://www.readbyqxmd.com/read/28630138/targeting-the-ras-palmitoylation-depalmitoylation-cycle-in-cancer
#5
REVIEW
David Tse Shen Lin, Nicholas G Davis, Elizabeth Conibear
The Ras proteins are well-known drivers of many cancers and thus represent attractive targets for the development of anticancer therapeutics. Inhibitors that disrupt the association of the Ras proteins with membranes by blocking the addition of the farnesyl lipid moiety to the Ras C-terminus failed in clinical trials. Here, we explore the possibility of targeting a second lipid modification, S-acylation, commonly referred to as palmitoylation, as a strategy to disrupt the membrane interaction of specific Ras isoforms...
June 19, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28630043/the-small-gtpases-k-ras-n-ras-and-h-ras-have-distinct-biochemical-properties-determined-by-allosteric-effects
#6
Christian W Johnson, Derion Reid, Jillian A Parker, Shores Salter, Ryan Knihtila, Petr Kuzmic, Carla Mattos
H-, K-, and N-Ras are small GTPases that are important in the control of cell proliferation, differentiation and survival, and their mutants occur frequently in human cancers. The G-domain, which catalyzes GTP hydrolysis and mediates downstream signaling, is 95% conserved between the Ras isoforms. Due to their very high sequence identity, biochemical studies done on H-Ras have been considered representative of all three Ras proteins. We show here that this is not a valid assumption. Using enzyme kinetic assays under identical conditions, we observed clear differences between the three isoforms in intrinsic catalysis of GTP by Ras in the absence and presence of the Ras-binding domain (RBD) of the C-Raf Kinase protein (Raf-RBD)...
June 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28629525/erythropoietin-regulation-by-angiotensin-ii
#7
Yong-Chul Kim, Ognoon Mungunsukh, Regina M Day
The renin-angiotensin system (RAS) is a key regulator of blood pressure and blood volume homeostasis. The RAS is primarily comprised of the precursor protein angiotensinogen and the two proteases, renin and angiotensin-converting enzyme (ACE). Angiotensin I (Ang I) is derived from angiotensinogen by renin, but appears to have no biological activity. In contrast, angiotensin II (Ang II) that has a variety of biological functions in the cells is converted from Ang I through removal of two-C-terminal residues by ACE...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28627617/sorafenib-controls-the-epithelial%C3%A2-mesenchymal-transition-of-ovarian-cancer-cells-via-egf-and-the-cd44%C3%A2-ha-signaling-pathway-in-a-cell-type%C3%A2-dependent-manner
#8
Ga Bin Park, Hyun-Suk Ko, Daejin Kim
Cluster of differentiation (CD) 44 and epidermal growth factor (EGF) are closely involved in cellular migration and have been used as stem cell markers. Although the hyaluronan (HA)‑binding CD44 is responsible for enhanced cellular motility, the mechanism underlying its actions in various cell types and clinical conditions have yet to be elucidated. In the present study, the multikinase inhibitor sorafenib was used to investigate the diverse effects of EGF stimulation on epithelial‑mesenchymal transition (EMT) in ovarian cancer cells using immunoblotting and reverse transcription‑polymerase chain reaction...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627346/-study-on-rac1-mapk-erk-pathway-mediated-mechanism-and-role-in-rats-with-ventilator-induced-lung-injury
#9
Guanghua Tao, Linghui Pan, Ren Jing, Fei Lin, Huijun Dai, Wanyun Ge
OBJECTIVE: To investigate the role of Ras-related C3 botulinum toxin substrate 1/mitogen-activated protein kinase/extracellular signal-regulated kinase (Rac1/MAPK/ERK) signal pathway in rats with ventilator induced lung injury (VILI) and its mechanism. METHODS: Thirty Sprague-Dawley (SD) rats were randomly divided into spontaneous respiration group, normal tidal volume (VT) group and high VT group with 10 rats in each group. The rats in spontaneous respiration group were kept their spontaneous breathing...
March 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28626963/exercise-training-modulates-the-hepatic-renin-angiotensin-system-in-fructose-fed-rats
#10
Eliete Dalla Corte Frantz, Renata Frauches Medeiros, Isabele Gomes Giori, Juliana Bittencourt Silveira Lima, Thais Bento-Bernardes, Thaiane Gadioli Gaique, Caroline Fernandes-Santos, Tiago Fernandes, Edilamar Menezes Oliveira, Carla Paulo Vieira, Carlos Adam Conte-Junior, Karen Jesus Oliveira, Antonio Claudio Lucas da Nóbrega
The renin-angiotensin system (RAS) has been implicated in the development of metabolic syndrome. We investigated whether the hepatic RAS is modulated by exercise training and if this modulation improves the deleterious effects of fructose overload in rats. Male Wistar rats were divided into (n = 8 each) control (CT), exercise control (CT-Ex), high fructose (HFr) and exercise high fructose (HFr-Ex) groups. Fructose-drinking rats received D-fructose (100 g L(-1) ). After two weeks, CT-Ex and HFr-Ex rats were assigned to a treadmill training protocol at moderate-intensity for eight weeks (60 min day(-1) , four days/week)...
June 19, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28626389/rac1-guides-porf-2-to-wnt-pathway-to-mediate-neural-stem-cell-proliferation
#11
Xi-Tao Yang, Guo-Hui Huang, Hong-Jiang Li, Zhao-Liang Sun, Nan-Jie Xu, Dong-Fu Feng
The molecular and cellular mechanisms underlying the anti-proliferative effects of preoptic regulator factor 2 (Porf-2) on neural stem cells (NSCs) remain largely unknown. Here, we found that Porf-2 inhibits the activity of ras-related C3 botulinum toxin substrate 1 (Rac1) protein in hippocampus-derived rat NSCs. Reduced Rac1 activity impaired the nuclear translocation of β-catenin, ultimately causing a repression of NSCs proliferation. Porf-2 knockdown enhanced NSCs proliferation but not in the presence of small molecule inhibitors of Rac1 or Wnt...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28625796/the-characterization-of-rheb-gene-and-its-responses-to-hypoxia-and-thermal-stresses-in-the-small-abalone-haliotis-diversicolor
#12
Lianghua He, Xin Zhang, Ying Huang, Huiping Yang, Yilei Wang, Ziping Zhang
RHEB (Ras Homolog Enriched in Brain) is a GTP-binding protein that is ubiquitously expressed in humans and other mammals. The protein is largely involved in the mechanistic target of rapamycin (mTOR) pathway, and regulates the cell cycle progression and growth. The goal of this study was to characterize the RHEB gene in the small abalone Haliotis diversicolor, and identify the responses of RHEB gene to stresses of hypoxia or/and thermal. The objectives were to: 1) clone the full-length cDNA RHEB gene in the H...
June 15, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28624843/expressions-of-ras-homolog-gene-family-member-a-rhoa-and-cyclooxygenase-2-cox-2-proteins-in-early-gastric-cancer-and-their-role-in-the-development-of-gastric-cancer
#13
Li Song, Yali Guo, Baohong Xu
BACKGROUND This research focused on detecting the expressions of RhoA and cyclooxygenase-2 (COX-2) proteins in early gastric cancer tissues and to explore their role in the development of gastric cancer. MATERIAL AND METHODS Surgically resected gastric cancer tissues and the paired normal paracancerous tissues were collected from 26 patients with early gastric cancer from January 2015 to November 2015. The expressions of RhoA and COX-2 proteins were detected by using RT-PCR and immunohistochemistry techniques, respectively...
June 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28624188/a-novel-single-strand-rnai-therapeutic-agent-targeting-the-pro-renin-receptor-suppresses-ocular-inflammation
#14
Atsuhiro Kanda, Erdal Tan Ishizuka, Atsushi Shibata, Takahiro Matsumoto, Hidekazu Toyofuku, Kousuke Noda, Kenichi Namba, Susumu Ishida
The receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to the (pro)renin receptor [(P)RR] dually activates the tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling. Here we revealed significant upregulation of prorenin and soluble (P)RR levels in the vitreous fluid of patients with uveitis compared to non-inflammatory controls, together with a positive correlation between these RAPS components and monocyte chemotactic protein-1 among several upregulated cytokines...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623606/marcks-is-necessary-for-oligodendrocyte-precursor-cell-maturation
#15
Zhao-Huan Zhang, Fan-Fei Ma, Hui Zhang, Xiao-Hui Xu
Oligodendrocyte precursor cell (OPC) development into myelinated oligodendrocytes demands vigorous membrane addition. Since myristoylated alanine-rich C-kinase substrate (MARCKS) reportedly contributes to Ras-associated protein (Rab)-10-associated vesicle insertion into neuronal membranes, we investigated the role of MARCKS in OPC maturation. We found that either knockdown of MARCKS or interruption of its interaction with Rab10 would cause a decrease of the cell membrane area during OPC development. Enhanced MARCKS phosphorylation by Nogo66 or myelin debris treatment inhibited OPC maturation, while its dephosphorylation by protein phosphatase 2 A activator D-erythro-sphingosine promoted OPC development in the presence of myelin debris...
June 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28623374/nucleotide-based-covalent-inhibitors-of-kras-can-only-be-efficient-in-vivo-if-they-bind-reversibly-with-gtp-like-affinity
#16
Matthias P Müller, Sadasivam Jeganathan, Angelika Heidrich, Jeremy Campos, Roger S Goody
Simple reversible competitive inhibition of nucleotide binding of GTP to Ras family GTPases has long been recognized as an unlikely approach to manipulating the activity of such proteins for experimental or therapeutic purposes. This is due to the high affinity of GTP to GTPases coupled with high cellular GTP concentrations, but also to problems of specificity for the highly conserved binding sites in GTPases. A recent approach suggested that these problems might be overcome by using GDP derivatives that can undergo a covalent reaction with disease specific mutants, in particular addressing inhibition of KRasG12C using GDP equipped with an electrophilic group at the β-phosphate...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621541/expanding-the-scope-of-electrophiles-capable-of-targeting-k-ras-oncogenes
#17
Lynn M McGregor, Meredith L Jenkins, Caitlin Kerwin, John E Burke, Kevan M Shokat
There is growing interest in reversible and irreversible covalent inhibitors that target noncatalytic amino acids in target proteins. With a goal of targeting oncogenic K-Ras variants (e.g., G12D) by expanding the types of amino acids that can be targeted by covalent inhibitors, we survey a set of electrophiles for their ability to label carboxylates. We functionalized an optimized ligand for the K-Ras switch II pocket with a set of electrophiles previously reported to react with carboxylates and characterized the ability of these compounds to react with model nucleophiles and oncogenic K-Ras proteins...
June 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/28621226/pten-a-potential-prognostic-marker-in-virus-induced-hepatocellular-carcinoma
#18
Ayesha Khalid, Tabinda Hussain, Sobia Manzoor, Muhammad Saalim, Saba Khaliq
PTEN is the second most frequently mutated tumor suppresser gene in cancers after p53. Genetic and epigenetic alterations in the PTEN gene and its regulatory regions have been reported in various studies. PTEN is a crucial downregulator of the pro-survival phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway and also suppresses insulin signaling. Failure to regulate these pathways leads to increase in cell proliferation and migration which in turn promotes tumorigenesis. PTEN underexpression is mediated by a variety of cytokines and stress kinases which seem to collectively induce the RAS/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28620131/exosomes-containing-differential-expression-of-microrna-and-mrna-in-osteosarcoma-that-can-predict-response-to-chemotherapy
#19
Ji-Feng Xu, Ya-Ping Wang, Shui-Jun Zhang, Yu Chen, Hai-Feng Gu, Xiao-Fan Dou, Bing Xia, Qing Bi, Shun-Wu Fan
A major challenge in osteosarcoma (OS) is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent. We developed a profiling strategy for serum exosomal microRNAs and mRNAs in OS patients with differential chemotherapeutic responses. Twelve miRNAs were up regulated and 18 miRNAs were under regulated significantly in OS patient with poor chemotherapeutic response when compared with those in good chemotherapeutic response (p<0...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615361/targeting-kras-dependent-tumors-with-azd4785-a-high-affinity-therapeutic-antisense-oligonucleotide-inhibitor-of-kras
#20
Sarah J Ross, Alexey S Revenko, Lyndsey L Hanson, Rebecca Ellston, Anna Staniszewska, Nicky Whalley, Sanjay K Pandey, Mitchell Revill, Claire Rooney, Linda K Buckett, Stephanie K Klein, Kevin Hudson, Brett P Monia, Michael Zinda, David C Blakey, Paul D Lyne, A Robert Macleod
Activating mutations in KRAS underlie the pathogenesis of up to 20% of human tumors, and KRAS is one of the most frequently mutated genes in cancer. Developing therapeutics to block KRAS activity has proven difficult, and no direct inhibitor of KRAS function has entered clinical trials. We describe the preclinical evaluation of AZD4785, a high-affinity constrained ethyl-containing therapeutic antisense oligonucleotide (ASO) targeting KRAS mRNA. AZD4785 potently and selectively depleted cellular KRAS mRNA and protein, resulting in inhibition of downstream effector pathways and antiproliferative effects selectively in KRAS mutant cells...
June 14, 2017: Science Translational Medicine
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