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Cellular Signalling

Subu Surendran Rajasekaran, Jaeyoon Kim, Gian-Carlo Gaboardi, Jesper Gromada, Stephen B Shears, Karen Tiago Dos Santos, Eduardo Lima Nolasco, Sabrina de Souza Ferreira, Christopher Illies, Martin Köhler, Chunfang Gu, Sung Ho Ryu, Joilson O Martins, Elisabetta Darè, Christopher J Barker, Per-Olof Berggren
Diphosphoinositol pentakisphosphate (IP7 ) is critical for the exocytotic capacity of the pancreatic β-cell, but its regulation by the primary instigator of β-cell exocytosis, glucose, is unknown. The high Km for ATP of the IP7 -generating enzymes, the inositol hexakisphosphate kinases (IP6K1 and 2) suggests that these enzymes might serve as metabolic sensors in insulin secreting β-cells and act as translators of disrupted metabolism in diabetes. To investigate this hypothesis, we now show that glucose stimulation, which increases the ATP/ADP ratio, leads to an early rise in IP7 concentration in β-cells...
March 6, 2018: Cellular Signalling
Hadjer Miloudi, Karen Leroy, Fabrice Jardin, Brigitte Sola
Primary mediastinal B-cell lymphoma (PMBL) is a distinct B-cell lymphoma subtype with unique clinicopathological and molecular features. PMBL cells are characterised by several genetic abnormalities that conduct to the constitutive activation of the Janus kinase 2/signal transducer and activator of transcription 6 (JAK2/STAT6) signalling pathway. Among recurrent genetic changes in PMBL, we previously reported that the XPO1 gene encoding exportin 1 that controls the nuclear export of cargo proteins and RNAs, is mutated (p...
March 1, 2018: Cellular Signalling
Tejinder Pal Khaket, Mahendra Pal Singh, Imran Khan, Monika Bhardwaj, Sun Chul Kang
As Autophagy is a pivotal mechanism of cancer cell survival and the development of chemotherapeutic resistance; therefore, new approaches are warranted for its targeting which may be fulfilled by cathepsins regulation. Amongst cathepsins, cathepsin C (CTSC) is highly expressed in various cancers and possesses significant therapeutic potential in autoimmune disorders; however, its role in colorectal cancer has not been explored. Herein, we aimed to investigate the role of CTSC in autophagy regulation mediated colorectal carcinoma cell proliferation...
March 1, 2018: Cellular Signalling
Chiachen Chen, Mary B Breslin, Michael S Lan
Neuroendocrine (NE) lung tumors account for 20% of total lung cancer cases and represent a subset of aggressive tumors with metastatic potential. High-risk NE lung cancer patients display disseminated disease, N-myc expression/amplification, and poorly differentiated tumors. In this study, we investigate the molecular mechanisms underlying a zinc-finger transcription factor, INSM1 in NE lung cancer. Our study revealed that INSM1 crosstalk with the Shh-PI3K/AKT-N-myc/Ascl1-MEK/ERK1/2 transcriptional network in NE lung cancer...
March 1, 2018: Cellular Signalling
Brandon H Kim, Alexey Pereverzev, Shuying Zhu, Abby Oi Man Tong, S Jeffrey Dixon, Peter Chidiac
Parathyroid hormone (PTH) activates the PTH/PTH-related peptide receptor (PTH1R) on osteoblasts and other target cells. Mechanical stimulation of cells, including osteoblasts, causes release of nucleotides such as ATP into the extracellular fluid. In addition to its role as an energy source, ATP serves as an agonist at P2 receptors and an allosteric regulator of many proteins. We investigated the effects of concentrations of extracellular ATP, comparable to those that activate low affinity P2X7 receptors, on PTH1R signaling...
March 1, 2018: Cellular Signalling
Ricardo Charles, Mohamed Bourmoum, Audrey Claing
Vascular smooth muscle cells (VSMC) can exhibit a contractile or a synthetic phenotype depending on the extracellular stimuli present and the composition of the extracellular matrix. Uncontrolled activation of the synthetic VSMC phenotype is however associated with the development of cardiovascular diseases. Here, we aimed to elucidate the role of the ARF GTPases in the regulation of VSMC dedifferentiation. First, we observed that the inhibition of the activation of ARF proteins with SecinH3, a blocker of the cytohesin ARF GEF family, reduced the ability of the cells to migrate and proliferate...
February 27, 2018: Cellular Signalling
Akshay Bareja, Shubham Patel, Conrad P Hodgkinson, Alan Payne, Victor J Dzau
The development of biased agonist drugs is widely recognized to be important for the treatment of many diseases, including cardiovascular disease. While GPCR biased agonism has been heavily characterized there is a distinct lack of information with respect to RTK biased agonism both in the identification of biased agonists as well as their attendant mechanisms. One such RTK, the Insulin-like Growth Factor 1 Receptor (IGF1R) plays an important role in a range of biological and disease processes. The micropeptide LL37 has been described as a biased agonist of the IGF1R...
February 27, 2018: Cellular Signalling
Chao-Tao Tang, Xiao-Lu Lin, Shan Wu, Qian Liang, Li Yang, Yun-Jie Gao, Zhi-Zheng Ge
NADPH Oxidase 4 (NOX4), a member of the NOX family, has emerged as a significant source of reactive oxygen species, playing an important role in tumor cell proliferation, apoptosis, and other physiological processes. However, the potential function of NOX4 in gastric cancer (GC) cell proliferation is yet unknown. The aim of this study was to illustrate whether NOX4 plays a role in regulating gastric cancer cell growth. First, the clinical information from 90 patients was utilized to explore the clinical value of NOX4 as a predictive tool for tumor size and prognosis...
February 26, 2018: Cellular Signalling
Patryk Janus, Katarzyna Szołtysek, Gracjana Zając, Tomasz Stokowy, Anna Walaszczyk, Wiesława Widłak, Bartosz Wojtaś, Bartłomiej Gielniewski, Marta Iwanaszko, Rosemary Brown, Simon Cockell, Neil D Perkins, Marek Kimmel, Piotr Widlak
The NF-κB transcription factors are activated via diverse molecular mechanisms in response to various types of stimuli. A plethora of functions associated with specific sets of target genes could be regulated differentially by this factor, affecting cellular response to stress including an anticancer treatment. Here we aimed to compare subsets of NF-κB-dependent genes induced in cells stimulated with a pro-inflammatory cytokine and in cells damaged by a high dose of ionizing radiation (4 and 10 Gy). The RelA-containing NF-κB species were activated by the canonical TNFα-induced and the atypical radiation-induced pathways in human osteosarcoma cells...
February 21, 2018: Cellular Signalling
Christina Klasen, Tamar Ziehm, Michael Huber, Yaw Asare, Aphrodite Kapurniotu, Idit Shachar, Jürgen Bernhagen, Omar El Bounkari
Macrophage migration inhibitory factor (MIF) is a chemokine-like inflammatory cytokine, which plays a pivotal role in the pathogenesis of inflammatory and cardiovascular diseases as well as cancer. We previously identified MIF as a novel B cell chemokine that promotes B cell migration through non-cognate interaction with the CXC chemokine receptor CXCR4 and CD74, the surface form of MHC class II invariant chain. In this study, we have analyzed the regulation of the MIF receptors under inflammatory conditions by investigating the impact of lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) on CD74 and CXCR4 expression in B lymphocytes...
February 21, 2018: Cellular Signalling
Kouhei Shimizu, Naoe Taira Nihira, Hiroyuki Inuzuka, Wenyi Wei
FBW7 is one of the most well characterized F-box proteins that serve as substrate recognition subunits of SCF (Skp1-Cullin 1-F-box proteins) E3 ubiquitin ligase complexes. SCFFBW7 plays key roles in regulating cell cycle progression, differentiation, and stem cell maintenance largely through targeting a broad range of oncogenic substrates for proteasome-dependent degradation. The identification of an increasing number of FBW7 substrates for ubiquitination, and intensive in vitro and in vivo studies have revealed a network of signaling components controlled by FBW7 that contributes to metabolic regulation as well as its tumor suppressor role...
February 20, 2018: Cellular Signalling
Matthew A Ingersoll, Yu-Wei Chou, Jamie S Lin, Ta-Chun Yuan, Dannah Miller, Yan Xie, Yaping Tu, Rebecca E Oberley-Deegan, Surinder K Batra, Ming-Fong Lin
Metastatic castration-resistant (CR) prostate cancer (PCa) is a lethal disease for which no effective treatment is currently available. p66Shc is an oxidase previously shown to promote androgen-independent cell growth through generation of reactive oxygen species (ROS) and elevated in clinical PCa and multiple CR PCa cell lines. We hypothesize p66Shc also increases the migratory activity of PCa cells through ROS and investigate the associated mechanism. Using the transwell assay, our study reveals that the level of p66Shc protein correlates with cell migratory ability across several PCa cell lines...
February 17, 2018: Cellular Signalling
Bingyan Shu, Yi Fang, Weichun He, Junwei Yang, Chunsun Dai
Lupus nephritis (LN) is a chronic autoimmune disorder. Here we try to identify the candidate genes in macrophages related to LN. We performed a systematic search in the Gene Expression Omnibus (GEO) database for microarray in human mononuclear cells and mouse macrophages of LN. The results of clustering and venn analysis of different GEO datasets showed that 8 genes were up-regulated and 2 genes down-regulated in samples from both human and mouse LN. The data from gene network and GO analysis revealed that CD38 and CCL2 were localized in the core of the network...
February 16, 2018: Cellular Signalling
Qi Xie, Xiaocui Chen, Yinghua Xu, Jing Liang, Fufang Wang, Ju Liu
Tube formation is one of the fundamental events required by angiogenesis and lymphangiogenesis. To date, there is little knowledge on the effects of hypoxia on tube formation of human dermal lymphatic endothelial cells (HDLECs). In this study, we found that tube formation of HDLECs was inhibited under hypoxic condition with decreased expressions of VEGF-D, CEACAM1 and Prox1 genes. However, hypoxia-induced inhibition of tube formation of HDLECs was reversed by conditional media from hypoxic tumor cells. After knockdown of CEACAM1 by siRNA transfection, tube formation of HDLECs was increased with elevated Prox1 expression, suggesting that CEACAM1 downregulates Prox1 and plays an inhibitory role in tube formation of HDLECs...
February 7, 2018: Cellular Signalling
Swetha Rudraiah, Rambon Shamilov, Brian J Aneskievich
Cell level inflammatory signalling is a combination of initiation at cell membrane receptors and modulation by cytoplasmic regulatory proteins. For keratinocytes, the predominant cell type in the epidermis, this would include toll-like receptors (TLR) and cytoplasmic proteins that propagate or dampen post-receptor signalling. We previously reported that increased levels of tumor necrosis factor α induced protein 3-interacting protein 1 (TNIP1) in HaCaT keratinocytes leads to decreased expression of stress response and inflammation-associated genes...
February 5, 2018: Cellular Signalling
Runmin Guo, Jiamei Jiang, Zhiliang Jing, Yonghua Chen, Zhizhou Shi, Baoping Deng
Insulin resistance is an important pathological hallmark of type 2 diabetes mellitus. Glucose-stimulated insulin secretion (GSIS) plays a key role in maintaining blood glucose levels within normal range. Impaired GSIS has been associated with type 2 diabetes, however, the underlying molecular mechanisms remain largely unknown. Cysteinyl leukotriene receptor 1 (cysLT1R) is an important G protein-coupled receptor mediating the biological functions of cysteinyl leukotrienes (cys-LTs). Little is known about the effects of cysLT1R in insulin secretion and pathogenesis of T2DM...
February 2, 2018: Cellular Signalling
Pooja Jadiya, Snober S Mir, Aamir Nazir
The accumulation of aggregate-prone proteins is a major representative of many neurological disorders, including Parkinson's disease (PD) wherein the cellular clearance mechanisms, such as the ubiquitin-proteasome and autophagy pathways are impaired. PD, known to be associated with multiple genetic and environmental factors, is characterized by the aggregation of α-synuclein protein and loss of dopaminergic neurons in midbrain. This disease is also associated with other cardiovascular ailments. Herein, we report our findings from studies on the effect of hyper and hypo-osmotic induced toxicity representing hyper and hypotensive condition as an extrinsic epigenetic factor towards modulation of Parkinsonism, using a genetic model Caenorhabditis elegans (C...
February 2, 2018: Cellular Signalling
Gennaro Bruno, Francesca Cencetti, Caterina Bernacchioni, Chiara Donati, Kira Vanessa Blankenbach, Dominique Thomas, Dagmar Meyer Zu Heringdorf, Paola Bruni
Skeletal muscle tissue retains a remarkable regenerative capacity due to the activation of resident stem cells that in pathological conditions or after tissue damage proliferate and commit themselves into myoblasts. These immature myogenic cells undergo differentiation to generate new myofibers or repair the injured ones, giving a strong contribution to muscle regeneration. Cytokines and growth factors, potently released after tissue injury by leukocytes and macrophages, are not only responsible of the induction of the initial inflammatory response, but can also affect skeletal muscle regeneration...
February 2, 2018: Cellular Signalling
Sunhwa Oh, Hyungjoo Kim, KeeSoo Nam, Incheol Shin
Egr-1 is known to function mainly as a tumor suppressor through direct regulation of multiple tumor suppressor genes. To determine the role of Egr-1 in breast tumors in vivo, we used mouse models of breast cancer induced by HER2/neu. We compared neu-overexpressing Egr-1 knockout mice (neu/Egr-1 KO) to neu-overexpressing Egr-1 wild type or heterozygote mice (neu/Egr-1 WT or neu/Egr-1 het) with regard to onset of tumor appearance and number of tumors per mouse. In addition, to examine the role of Egr-1 in vitro, we established neu/Egr-1 WT and KO tumor cell lines derived from breast tumors developed in each mouse...
February 2, 2018: Cellular Signalling
Kira G Slepchenko, Justin M Holub, Yang V Li
Protein kinase C delta (PKCδ) is a Ser/Thr-specific kinase involved in many fundamental cellular processes including growth, differentiation and apoptosis. PKCδ is expressed ubiquitously in all known cell types, and can be activated by diacylglycerol, phorbol esters and other kinases. Multiple lines of evidence have indicated that the mode of activation greatly influences the role PKCδ plays in cellular function. Divalent metal ions, such as zinc are released as a response to cellular stress and injury, often resulting in oxidative damage and cell death...
February 1, 2018: Cellular Signalling
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