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Cell Communication and Signaling: CCS

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https://www.readbyqxmd.com/read/28212658/c-met-expression-and-activity-in-urogenital-cancers-novel-aspects-of-signal-transduction-and-medical-implications
#1
REVIEW
Ralf Hass, Susanne Jennek, Yuanyuan Yang, Karlheinz Friedrich
C-Met is a receptor tyrosine kinase with multiple functions throughout embryonic development, organogenesis and wound healing and is expressed in various epithelia. The ligand of c-Met is Hepatocyte Growth Factor (HGF) which is secreted among others by mesenchymal stroma/stem (MSC) cells.Physiological c-Met functions are centred around processes that underly cellular motility and invasive growth. Aberrant c-Met expression and activity is observed in numerous cancers and makes major contributions to cell malignancy...
February 17, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28143584/translationally-controlled-tumour-protein-tctp-is-induced-early-in-human-colorectal-tumours-and-contributes-to-the-resistance-of-hct116-colon-cancer-cells-to-5-fu-and-oxaliplatin
#2
Ulrich-Axel Bommer, Kara L Vine, Prianka Puri, Martin Engel, Lisa Belfiore, Karen Fildes, Marijka Batterham, Alistair Lochhead, Morteza Aghmesheh
BACKGROUND: Translationally controlled tumour protein TCTP is an anti-apoptotic protein frequently overexpressed in cancers, where high levels are often associated with poor patient outcome. TCTP may be involved in protecting cancer cells against the cytotoxic action of anti-cancer drugs. Here we study the early increase of TCTP levels in human colorectal cancer (CRC) and the regulation of TCTP expression in HCT116 colon cancer cells, in response to treatment with the anti-cancer drugs 5-FU and oxaliplatin...
February 1, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28122581/acute-myeloid-leukemia-strategies-and-challenges-for-targeting-oncogenic-hedgehog-gli-signaling
#3
REVIEW
Fritz Aberger, Evelyn Hutterer, Christina Sternberg, Pedro J Del Burgo, Tanja N Hartmann
Treatment of acute myeloid leukemia (AML), an aggressive and heterogeneous hematological malignancy, remains a challenge. Despite advances in our understanding of the complex genetics and biology of AML pathophysiology, these findings have been translated to the clinic with only limited success, and poor outcomes persist for the majority of patients. Thus, novel treatment strategies are clearly needed for achieving deeper and prolonged remissions and for avoiding the development of resistance. Due to its profound role in (cancer) stem cell biology and differentiation, the Hedgehog (HH)/Glioma-associated Oncogene Homolog (GLI) signaling pathway may be an attractive novel therapeutic target in AML...
January 25, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28122577/the-id-protein-family-in-developmental-and-cancer-associated-pathways
#4
REVIEW
Cornelia Roschger, Chiara Cabrele
Inhibitors of DNA binding and cell differentiation (Id) proteins are members of the large family of the helix-loop-helix (HLH) transcription factors, but they lack any DNA-binding motif. During development, the Id proteins play a key role in the regulation of cell-cycle progression and cell differentiation by modulating different cell-cycle regulators both by direct and indirect mechanisms. Several Id-protein interacting partners have been identified thus far, which belong to structurally and functionally unrelated families, including, among others, the class I and II bHLH transcription factors, the retinoblastoma protein and related pocket proteins, the paired-box transcription factors, and the S5a subunit of the 26 S proteasome...
January 25, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28103956/unraveling-the-regulation-of-mtorc2-using-logical-modeling
#5
Kirsten Thobe, Christine Sers, Heike Siebert
BACKGROUND: The mammalian target of rapamycin (mTOR) is a regulator of cell proliferation, cell growth and apoptosis working through two distinct complexes: mTORC1 and mTORC2. Although much is known about the activation and inactivation of mTORC1, the processes controlling mTORC2 remain poorly characterized. Experimental and modeling studies have attempted to explain the regulation of mTORC2 but have yielded several conflicting hypotheses. More specifically, the Phosphoinositide 3-kinase (PI3K) pathway was shown to be involved in this process, but the identity of the kinase interacting with and regulating mTORC2 remains to be determined (Cybulski and Hall, Trends Biochem Sci 34:620-7, 2009)...
January 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28100240/reactivation-of-dormant-anti-tumor-immunity-a-clinical-perspective-of-therapeutic-immune-checkpoint-modulation
#6
REVIEW
Richard Greil, Evelyn Hutterer, Tanja Nicole Hartmann, Lisa Pleyer
In favor of their outgrowth, cancer cells must resist immune surveillance and edit the immune response. Cancer immunoediting is characterized by fundamental changes in the cellular composition and the inflammatory cytokine profiles in the microenvironment of the primary tumor and metastatic niches, with an ever increasing complexity of interactions between tumor cells and the immune system. Recent data suggest that genetic instability and immunoediting are not necessarily disparate processes. Increasing mutational load may be associated with multiple neoepitopes expressed by the tumor cells and thus increased chances for the immune system to recognize and combat these cells...
January 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28069057/bacterial-serine-protease-htra-as-a-promising-new-target-for-antimicrobial-therapy
#7
EDITORIAL
Silja Wessler, Gisbert Schneider, Steffen Backert
Recent studies have demonstrated that the bacterial chaperone and serine protease high temperature requirement A (HtrA) is closely associated with the establishment and progression of several infectious diseases. HtrA activity enhances bacterial survival under stress conditions, but also has direct effects on functions of the cell adhesion protein E-cadherin and extracellular matrix proteins, including fibronectin and proteoglycans. Although HtrA cannot be considered as a pathogenic factor per se, it exhibits favorable characteristics making HtrA a potentially attractive drug target to combat various bacterial infections...
January 10, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28073378/hectd1-controls-the-protein-level-of-iqgap1-to-regulate-the-dynamics-of-adhesive-structures
#8
Xiaoli Shen, Zanhui Jia, Donato D'Alonzo, Xinggang Wang, Elisabeth Bruder, Fabienne Hélène Emch, Christian De Geyter, Hong Zhang
BACKGROUND: Cell migration including collective cell movement and individual cell migration are crucial factors in embryogenesis. During the spreading/migration of cells, several types of adhesive structures physically interacting with the extracellular matrix (ECM) or with another cell have been described and the formation and maturation of adhesion structures are coordinated, however the molecular pathways involved are still not fully understood. RESULTS: We generated a mouse embryonic fibroblast line (MEF) from homozygous mutant (Hectd1 (R/R) , Hectd1 (Gt(RRC200)) ) mouse of the E3 ubiquitin ligase for inhibin B receptor (Hectd1)...
January 5, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28073373/t-cell-exhaustion-from-pathophysiological-basics-to-tumor-immunotherapy
#9
REVIEW
Kemal Catakovic, Eckhard Klieser, Daniel Neureiter, Roland Geisberger
The immune system is capable of distinguishing between danger- and non-danger signals, thus inducing either an appropriate immune response against pathogens and cancer or inducing self-tolerance to avoid autoimmunity and immunopathology. One of the mechanisms that have evolved to prevent destruction by the immune system, is to functionally silence effector T cells, termed T cell exhaustion, which is also exploited by viruses and cancers for immune escape In this review, we discuss some of the phenotypic markers associated with T cell exhaustion and we summarize current strategies to reinvigorate exhausted T cells by blocking these surface marker using monoclonal antibodies...
January 5, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28057038/aldose-reductase-mediates-endothelial-cell-dysfunction-induced-by-high-uric-acid-concentrations
#10
Zhiyong Huang, Quan Hong, Xueguang Zhang, Wenzhen Xiao, Liyuan Wang, Shaoyuan Cui, Zhe Feng, Yang Lv, Guangyan Cai, Xiangmei Chen, Di Wu
BACKGROUND: Uric acid (UA) is an antioxidant found in human serum. However, high UA levels may also have pro-oxidant functions. According to previous research, aldose reductase (AR) plays a vital role in the oxidative stress-related complications of diabetes. We sought to determine the mechanism by which UA becomes deleterious at high concentrations as well as the effect of AR in this process. METHOD: Endothelial cells were divided into three groups cultured without UA or with 300 μM or 600 μM UA...
January 5, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/27282631/transferring-intercellular-signals-and-traits-between-cancer-cells-extracellular-vesicles-as-homing-pigeons
#11
REVIEW
Giulia Cesi, Geoffroy Walbrecq, Christiane Margue, Stephanie Kreis
Extracellular vesicles are cell-derived vesicles, which can transport various cargos out of cells. From their cell of origin, the content molecules (proteins, non-coding RNAs including miRNAs, DNA and others) can be delivered to neighboring or distant cells and as such extracellular vesicles can be regarded as vehicles of intercellular communication or "homing pigeons". Extracellular vesicle shuttling is able to actively modulate the tumor microenvironment and can partake in tumor dissemination. In various diseases, including cancer, levels of extracellular vesicle secretion are altered resulting in different amounts and/or profiles of detectable vesicular cargo molecules and these distinct content profiles are currently being evaluated as biomarkers...
June 10, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/27206658/differential-lyn-dependence-of-the-ship1-deficient-mast-cell-phenotype
#12
Susana M Nunes de Miranda, Thomas Wilhelm, Michael Huber, Carolin N Zorn
BACKGROUND: Antigen (Ag)/IgE-mediated mast cell (MC) responses play detrimental roles in allergic diseases. MC activation via the high-affinity receptor for IgE (FcεRI) is controlled by the Src family kinase Lyn. Lyn-deficient (-/-) bone marrow-derived MCs (BMMCs) have been shown by various laboratories to exert stronger activation of the PI3K pathway, degranulation, and production of pro-inflammatory cytokines compared to wild-type (wt) cells. This mimics the phenotype of BMMCs deficient for the SH2-containing inositol-5'-phosphatase 1 (SHIP1)...
May 20, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/27170143/the-arabidopsis-cyclic-nucleotide-interactome
#13
Lara Donaldson, Stuart Meier, Christoph Gehring
BACKGROUND: Cyclic nucleotides have been shown to play important signaling roles in many physiological processes in plants including photosynthesis and defence. Despite this, little is known about cyclic nucleotide-dependent signaling mechanisms in plants since the downstream target proteins remain unknown. This is largely due to the fact that bioinformatics searches fail to identify plant homologs of protein kinases and phosphodiesterases that are the main targets of cyclic nucleotides in animals...
May 11, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/27048167/the-new-dis-order-in-rna-regulation
#14
REVIEW
Aino I Järvelin, Marko Noerenberg, Ilan Davis, Alfredo Castello
RNA-binding proteins play a key role in the regulation of all aspects of RNA metabolism, from the synthesis of RNA to its decay. Protein-RNA interactions have been thought to be mostly mediated by canonical RNA-binding domains that form stable secondary and tertiary structures. However, a number of pioneering studies over the past decades, together with recent proteome-wide data, have challenged this view, revealing surprising roles for intrinsically disordered protein regions in RNA binding. Here, we discuss how disordered protein regions can mediate protein-RNA interactions, conceptually grouping these regions into RS-rich, RG-rich, and other basic sequences, that can mediate both specific and non-specific interactions with RNA...
April 6, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/26936767/motif-mediated-protein-protein-interactions-as-drug-targets
#15
REVIEW
Carles Corbi-Verge, Philip M Kim
Protein-protein interactions (PPI) are involved in virtually every cellular process and thus represent an attractive target for therapeutic interventions. A significant number of protein interactions are frequently formed between globular domains and short linear peptide motifs (DMI). Targeting these DMIs has proven challenging and classical approaches to inhibiting such interactions with small molecules have had limited success. However, recent new approaches have led to the discovery of potent inhibitors, some of them, such as Obatoclax, ABT-199, AEG-40826 and SAH-p53-8 are likely to become approved drugs...
March 2, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/26912052/axitinib-and-sorafenib-are-potent-in-tyrosine-kinase-inhibitor-resistant-chronic-myeloid-leukemia-cells
#16
Sebastian Halbach, Zehan Hu, Christine Gretzmeier, Julia Ellermann, Franziska U Wöhrle, Jörn Dengjel, Tilman Brummer
BACKGROUND: Chronic myeloid leukemia (CML) is driven by the fusion kinase Bcr-Abl. Bcr-Abl tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), revolutionized CML therapy. Nevertheless, about 20 % of CMLs display primary or acquired TKI resistance. TKI resistance can be either caused by mutations within the Bcr-Abl kinase domain or by aberrant signaling by its effectors, e.g. Lyn or Gab2. Bcr-Abl mutations are frequently observed in TKI resistance and can only in some cases be overcome by second line TKIs...
February 24, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/26861207/feedback-activation-of-neurofibromin-terminates-growth-factor-induced-ras-activation
#17
Anne Hennig, Robby Markwart, Katharina Wolff, Katja Schubert, Yan Cui, Ian A Prior, Manuel A Esparza-Franco, Graham Ladds, Ignacio Rubio
BACKGROUND: Growth factors induce a characteristically short-lived Ras activation in cells emerging from quiescence. Extensive work has shown that transient as opposed to sustained Ras activation is critical for the induction of mitogenic programs. Mitogen-induced accumulation of active Ras-GTP results from increased nucleotide exchange driven by the nucleotide exchange factor Sos. In contrast, the mechanism accounting for signal termination and prompt restoration of basal Ras-GTP levels is unclear, but has been inferred to involve feedback inhibition of Sos...
February 9, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/27582276/epigenetic-regulation-of-transcription-factor-promoter-regions-by-low-dose-genistein-through-mitogen-activated-protein-kinase-and-mitogen-and-stress-activated-kinase-1-nongenomic-signaling
#18
Linda Yu, Kyle Ham, Xiaohua Gao, Lysandra Castro, Yitang Yan, Grace E Kissling, Charles J Tucker, Norris Flagler, Ray Dong, Trevor K Archer, Darlene Dixon
BACKGROUND: The phytoestrogen, genistein at low doses nongenomically activates mitogen-activated protein kinase p44/42 (MAPKp44/42) via estrogen receptor alpha (ERα) leading to proliferation of human uterine leiomyoma cells. In this study, we evaluated if MAPKp44/42 could activate downstream effectors such as mitogen- and stress-activated protein kinase 1 (MSK1), which could then epigenetically modify histone H3 by phosphorylation following a low dose (1 μg/ml) of genistein. RESULTS: Using hormone-responsive immortalized human uterine leiomyoma (ht-UtLM) cells, we found that genistein activated MAPKp44/42 and MSK1, and also increased phosphorylation of histone H3 at serine10 (H3S10ph) in ht-UtLM cells...
31, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/27465248/role-of-pkctheta-in-macrophage-mediated-immune-response-to-salmonella-typhimurium-infection-in-mice
#19
Christa Pfeifhofer-Obermair, Karin Albrecht-Schgoer, Sebastian Peer, Manfred Nairz, Kerstin Siegmund, Victoria Klepsch, David Haschka, Nikolaus Thuille, Natascha Hermann-Kleiter, Thomas Gruber, Günter Weiss, Gottfried Baier
BACKGROUND: The serine/threonine protein kinase C (PKC) theta has been firmly implicated in T cell-mediated immunity. Because its role in macrophages has remained undefined, we employed PKCtheta-deficient (PKCtheta (-/-)) mice in order to investigate if PKCtheta plays a role in macrophage-mediated immune responses during bacterial infections. RESULTS: Our results demonstrate that PKCtheta plays an important role in host defense against the Gram-negative, intracellular bacterium Salmonella typhimurium, as reflected both by markedly decreased survival and a significantly enhanced number of bacteria in spleen and liver of PKCtheta (-/-) mice, when compared to wild-type mice...
28, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/27784296/-inverse-signaling-of-the-transmembrane-chemokine-cxcl16-contributes-to-proliferative-and-anti-apoptotic-effects-in-cultured-human-meningioma-cells
#20
Kirsten Hattermann, Kareen Bartsch, Henrike H Gebhardt, H Maximilian Mehdorn, Michael Synowitz, Anne Dorothée Schmitt, Rolf Mentlein, Janka Held-Feindt
BACKGROUND: Chemokines and their receptors play a decisive role in tumor progression and metastasis. We recently found a new signaling mechanism in malignant glioma cells mediated by transmembrane chemokines that we termed "inverse signaling". According to this hypothesis, soluble (s)-CXCL16 binds to the surface-expressed transmembrane (tm) -CXCL16, and induces signaling and different biological effects in the stimulated cells, so that the transmembrane ligand itself acts as a receptor for its soluble counterpart...
27, 2016: Cell Communication and Signaling: CCS
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