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https://www.readbyqxmd.com/read/29163769/yap1-is-essential-for-tumor-growth-and-is-a-potential-therapeutic-target-for-egfr-dependent-lung-adenocarcinomas
#1
Ting-Fang Lee, Yu-Chi Tseng, Wei-Chin Chang, Yi-Chen Chen, Yu-Rung Kao, Teh-Ying Chou, Chao-Chi Ho, Cheng-Wen Wu
Epidermal growth factor receptor (EGFR) mutations are found in lung adenocarcinomas leading to tumor cells proliferation and survival. EGFR tyrosine kinase inhibitors (TKIs) that block EGFR activity are effective therapeutics for EGFR-mutant lung adenocarcinoma patients, but TKI-resistance inevitably occurs. The YES-associated protein (YAP1) transcription coactivator has been implicated as an oncogene and is amplified in human cancers and provides tumor cells strong proliferation and survival cues. This study investigated the roles of YAP1 in lung adenocarcinoma by exploring its regulation and functions mediated by EGFR signaling...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163047/biphasic-regulation-of-caveolin-1-gene-expression-by-fluoxetine-in-astrocytes-opposite-effects-of-pi3k-akt-and-mapk-erk-signaling-pathways-on-c-fos
#2
Baoman Li, Shu Jia, Tingting Yue, Li Yang, Chen Huang, Alexej Verkhratsky, Liang Peng
Previously, we reported that fluoxetine acts on 5-HT2B receptor and induces epidermal growth factor receptor (EGFR) transactivation in astrocytes. Recently, we have found that chronic treatment with fluoxetine regulates Caveolin-1 (Cav-1)/PTEN/PI3K/AKT/glycogen synthase kinase 3β (GSK-3β) signaling pathway and glycogen content in primary cultures of astrocytes with bi-phasic concentration dependence. At low concentrations fluoxetine down-regulates Cav-1 gene expression, decreases membrane content of PTEN, increases PI3K activity and increases phosphorylation of GSK-3β and increases its activity; at high concentrations fluoxetine acts on PTEN/PI3K/AKT/GSK-3β in an inverse fashion...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29162704/tropomyosin-related-kinase-c-trkc-enhances-podocyte-migration-by-erk-mediated-wave2-activation
#3
Sascha Gromnitza, Carolin Lepa, Thomas Weide, Albrecht Schwab, Hermann Pavenstädt, Britta George
Podocyte malfunction is central to glomerular diseases and is marked by defective podocyte intercellular junctions and actin cytoskeletal dynamics. Podocytes share many morphologic features with neurons, so that similar sets of proteins appear to regulate cell process formation. One such protein is the tropomyosin-related kinase C (TrkC). TrkC deficiency in mice leads to proteinuria as a surrogate of defective kidney filter function. Activation of endogenous TrkC by its ligand neurotrophin-3 resulted in increased podocyte migration-a surrogate of podocyte actin dynamics in vivo Employing a mutagenesis approach, we found that the Src homologous and collagen-like (Shc) binding site Tyr(516) within the TrkC cytoplasmic domain was necessary for TrkC-induced migration of podocytes...
November 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29157819/pro-angiogenic-effects-of-ilexsaponin-a1-on-human-umbilical-vein-endothelial-cells-in-vitro-and-zebrafish-in-vivo
#4
Jingjing Li, Jinming Zhang, Liang Zou, Simon Ming-Yuen Lee, Cui Yang, Sai-Wang Seto, George Pak-Heng Leung
BACKGROUND: Ilexsaponin A1 is the major bioactive ingredient of Ilex pubescens Hook. et Arn. This plant has been conventionally used in Traditional Chinese Medicine for the treatment of cardiovascular diseases including stroke, coronary arterial disease, and peripheral vascular diseases. PURPOSE: To investigate the pro-angiogenic effect of Ilexsaponin A1 and its mechanism of action. STUDY DESIGN: Human umbilical vein endothelial cells (HUVECs) and transgenic zebrafish Tg(fli1:EGFP) were employed as an in vitro and in vivo model respectively...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29156825/targeting-p-selectin-blocks-neuroblastoma-growth
#5
Riitta Nolo, Shelley Herbrich, Arvind Rao, Patrick Zweidler-McKay, Sankaranarayanan Kannan, Vidya Gopalakrishnan
Selectins and their ligands have been implicated in tumor growth and progression in carcinomas, but their role in neuroblastoma has not been systematically examined. In the current study we evaluated L-, P- and E-selectin binding to neuroblastoma cells and the expression of some of their known ligands, namely CD44, CD24 and P-selectin glycoprotein ligand-1 (PSGL-1). Genetic loss of PSGL-1 or CD24 and pharmacological inhibition of P-selectin reduced P-selectin binding to neuroblastoma cells in vitro. Targeting P-selectin using specific antibodies promoted a significant reduction in the growth of neuroblastoma tumors in vivo...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155031/the-involvement-of-suppressor-of-cytokine-signaling-6-socs6-in-immune-response-of-chinese-mitten-crab-eriocheir-sinensis
#6
Chen Qu, Qingsong Xu, Mengmeng Lu, Feifei Wang, Zhaoqun Liu, Dongyang Liu, Wen Yang, Qilin Yi, Lingling Wang, Linsheng Song
Suppressor of cytokine signaling (SOCS) is a family of cytokine-inducible negative regulators of cytokine signaling and it plays a crucial role in various physiological processes. In the present study, the full-length cDNA of a SOCS (designated as EsSOCS6) was cloned from Chinese mitten crab Eriocheir sinensis. The open reading frame of EsSOCS6 cDNA was of 1266 bp, which encoded a polypeptide of 421 amino acid residues. There were two typically conserved SOCS family domains in EsSOCS6, including a central Src homology 2 (SH2) domain and a C-terminal SOCS box...
November 15, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29152606/ethanol-induced-steatosis-involves-impairment-of-lipophagy-associated-with-reduced-dynamin2-activity
#7
Karuna Rasineni, Terrence M Donohue, Paul G Thomes, Li Yang, Dean J Tuma, Mark A McNiven, Carol A Casey
Background: Lipid droplets (LDs), the organelles central to alcoholic steatosis, are broken down by lipophagy, a specialized form of autophagy. Here, we hypothesize that ethanol administration retards lipophagy by down-regulating Dynamin 2 (Dyn2), a protein that facilitates lysosome re-formation, contributing to hepatocellular steatosis. Methods: Primary hepatocytes were isolated from male Wistar rats fed Lieber-DeCarli control or EtOH liquid diets for 6-8 wk. Hepatocytes were incubated in complete medium (fed) or nutrient-free medium (fasting) with or without the Dyn2 inhibitor Dynasore or the Src inhibitor SU6656...
August 2017: Hepatol Commun
https://www.readbyqxmd.com/read/29152154/cortactin-in-cancer-cell-migration-and-invasion
#8
REVIEW
Miao Yin, Wenqing Ma, Liguo An
Cortactin, a substrate of sarcoma (Src) kinases, is an actin-binding protein that is involved in cytoskeletal regulation, and is frequently overexpressed in cancer cells. Binding to the actin related protein 2/3 (Arp2/3) complex stimulates cortactin activity, which promotes F-actin nucleation and assembly. Cortactin promotes cancer cell migration and invasion, and plays a pivotal role in invadopodia formation and extra cellular matrix degradation. Overexpression of cortactin, by amplification of the chromosomal band 11q13, increases tumor aggressiveness...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152059/gzd824-suppresses-the-growth-of-human-b-cell-precursor-acute-lymphoblastic-leukemia-cells-by-inhibiting-the-src-kinase-and-pi3k-akt-pathways
#9
Wei Ye, Zhiwu Jiang, Xiaoyun Lu, Xiaomei Ren, Manman Deng, Shouheng Lin, Yiren Xiao, Simiao Lin, Suna Wang, Baiheng Li, Yi Zheng, Peilong Lai, Jianyu Weng, Donghai Wu, Yuguo Ma, Xudong Chen, Zhesheng Wen, Yaoyu Chen, Xiaoyan Feng, Yangqiu Li, Pentao Liu, Xin Du, Duanqing Pei, Yao Yao, Bing Xu, Ke Ding, Peng Li
Available therapeutic options for advanced B cell precursor acute lymphoblastic leukemia (pre-B ALL) are limited. Many lead to neutropenia, leaving patients at risk of life-threatening infections and result in bad outcomes. New treatment options are needed to improve overall survival. We previously showed that GZD824, a novel BCR-ABL tyrosine kinase inhibitor, has anti-tumor activity in Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia cells and tumor models. Here, we show that GZD824 decreases cell viability, induces cell-cycle arrest, and causes apoptosis in pre-B ALL cells...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150433/tyrosine-phosphorylation-of-munc18-1-inhibits-synaptic-transmission-by-preventing-snare%C3%A2-assembly
#10
Marieke Meijer, Bernhard Dörr, Hanna Ca Lammertse, Chrysanthi Blithikioti, Jan Rt van Weering, Ruud Fg Toonen, Thomas H Söllner, Matthijs Verhage
Tyrosine kinases are important regulators of synaptic strength. Here, we describe a key component of the synaptic vesicle release machinery, Munc18-1, as a phosphorylation target for neuronal Src family kinases (SFKs). Phosphomimetic Y473D mutation of a SFK phosphorylation site previously identified by brain phospho-proteomics abolished the stimulatory effect of Munc18-1 on SNARE complex formation ("SNARE-templating") and membrane fusion in vitro Furthermore, priming but not docking of synaptic vesicles was disrupted in hippocampal munc18-1-null neurons expressing Munc18-1Y473D Synaptic transmission was temporarily restored by high-frequency stimulation, as well as by a Munc18-1 mutation that results in helix 12 extension, a critical conformational step in vesicle priming...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29146887/targeted-therapy-of-gastroenteropancreatic-neuroendocrine-tumours-preclinical-strategies-and-future-targets
#11
Elke Tatjana Aristizabal Prada, Christoph J Auernhammer
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mTOR-inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression free survival due to tumor resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP-system are needed. This paper reviews preclinical research models and signaling pathways in NETs of the GEP-system...
November 16, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29141923/src-family-kinase-inhibitors-blunt-the-pacap-induced-pac1-receptor-endocytosis-phosphorylation-of-erk-and-increase-in-cardiac-neuron-excitability
#12
John D Tompkins, Todd A Clason, Thomas R Buttolph, Beatrice M Girard, Anne K Linden, Jean C Hardwick, Laura A Merriam, Victor May, Rodney L Parsons
Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors (Adcyap1r1) significantly increases excitability of guinea pig cardiac neurons. This modulation of excitability is mediated in part by plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades. However, additional mechanisms responsible for the enhanced excitability are activated following internalization of the PAC1 receptor and endosomal signaling. Src family kinases play critical roles mediating endocytosis of many trophic factor and G-protein coupled receptors...
November 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29140740/upregulation-of-tyrosine-kinase-fyn-in-human-thyroid-carcinoma-role-in-modulating-tumor-cell-proliferation-invasion-and-migration
#13
Jing Zheng, Huiling Li, Dongting Xu, Huijuan Zhu
Tyrosine kinase FYN-a member of the SRC family of kinases-is associated with mediating mitogenic signals and regulating cell cycle entry, growth, and proliferation. It was hypothesized that FYN is upregulated in thyroid carcinoma, which plays a critical role in tumorigenesis. FYN expression level in thyroid carcinoma tissue and tumor cell lines was determined. Also, the effects of FYN on thyroid cancer (TC) growth, signaling, cell cycle, and apoptosis were evaluated in vitro. FYN was knocked down in thyroid cancer cells (TPC-1) by siRNA to investigate the effects on cell proliferation, invasion, and migration...
November 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29137326/overexpression-of-carbonic-anhydrase-ix-induces-cell-motility-by-activating-matrix-metalloproteinase-9-in-human-oral-squamous-cell-carcinoma-cells
#14
Jia-Sin Yang, Chiao-Wen Lin, Yi-Hsien Hsieh, Ming-Hsien Chien, Chun-Yi Chuang, Shun-Fa Yang
Oral cancer is a solid malignant tumor that is prone to occur following hypoxia. There are no clear studies showing a link between hypoxia and oral carcinogenesis. Carbonic anhydrase IX (CAIX), which is a hypoxia-induced transmembrane protein, is highly expressed in various types of human cancer. However, the effects of CAIX on the metastasis of human oral cancer cells and the underlying molecular mechanisms have not been clarified. In this study, we observed that CAIX overexpression increased the migratory and invasive abilities of SCC-9 and SAS cells...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136335/sii-ang-ii-potentiates-insulin-receptor-signalling-and-glycogen-synthesis-in-hepatocytes
#15
Samra Joke Sanni, Christina Lyngsø, Steen Gammeltoft, Jakob Lerche Hansen
The angiotensin II type I receptor (AT1R) is involved in the regulation of cardiovascular function. Excessive activation of AT1R by angiotensin II (Ang II) leads to cardiovascular disease and may be involved in the development of insulin resistance and diabetes. Functionally selective Ang II analogues, such as the [Sar1, Ile4, Ile8]-angiotensin II (SII Ang II) analogue that only activates a subset of signalling networks have been demonstrated to have beneficial effects on cardiovascular function in certain settings, including lowering blood pressure and increasing cardiac performance...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29136005/a-17-molecule-set-as-a-predictor-of-complete-response-to-neoadjuvant-chemotherapy-with-docetaxel-cisplatin-and-5-fluorouracil-in-esophageal-cancer
#16
Hajime Fujishima, Shoichi Fumoto, Tomotaka Shibata, Kohei Nishiki, Yoshiyuki Tsukamoto, Tsuyoshi Etoh, Masatsugu Moriyama, Norio Shiraishi, Masafumi Inomata
BACKGROUND: Recently, neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil (NAC-DCF) was identified as a novel strong regimen with a high rate of pathological complete response (pCR) in advanced esophageal cancer in Japan. Predicting pCR will contribute to the therapeutic strategy and the prevention of surgical invasion. However, a predictor of pCR after NAC-DCF has not yet been developed. The aim of this study was to identify a novel predictor of pCR in locally advanced esophageal cancer treated with NAC-DCF...
2017: PloS One
https://www.readbyqxmd.com/read/29133485/pyk2-and-fak-differentially-regulate-invadopodia-formation-and-function-in-breast-cancer-cells
#17
Alessandro Genna, Stefanie Lapetina, Nikola Lukic, Shams Twafra, Tomer Meirson, Ved P Sharma, John S Condeelis, Hava Gil-Henn
The nonreceptor tyrosine kinase Pyk2 is highly expressed in invasive breast cancer, but the mechanism by which it potentiates tumor cell invasiveness is unclear at present. Using high-throughput protein array screening and bioinformatic analysis, we identified cortactin as a novel substrate and interactor of proline-rich tyrosine kinase 2 (Pyk2). Pyk2 colocalizes with cortactin to invadopodia of invasive breast cancer cells, where it mediates epidermal growth factor-induced cortactin tyrosine phosphorylation both directly and indirectly via Src-mediated Abl-related gene (Arg) activation, leading to actin polymerization in invadopodia, extracellular matrix degradation, and tumor cell invasion...
November 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29132432/ac-93253-iodide-a-novel-src-inhibitor-suppresses-nsclc-progression-by-modulating-multiple-src-related-signaling-pathways
#18
Yi-Hua Lai, Sih-Yin Lin, Yu-Shan Wu, Huei-Wen Chen, Jeremy J W Chen
BACKGROUND: The tyrosine kinase Src is involved in the progression of many cancers. Moreover, inhibiting Src activity has been shown to obstruct several signaling pathways regulated by the EGFR. Thus, Src is a valuable target molecule in drug development. The purpose of this study was to identify compounds that directly or indirectly modulate Src to suppress lung cancer cell growth and motility and to investigate the molecular mechanisms underlying the effects of these compounds. METHODS: Human non-small cell lung cancer (NSCLC) cell lines (PC9, PC9/gef, A549, and H1975) with different EGFR statuses were tested by cytotoxicity and proliferation assays after AC-93253 iodide treatment...
November 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29130514/involvement-of-src-signaling-in-the-synergistic-effect-between-cisplatin-and-digoxin-on-cancer-cell-viability
#19
Duane Gischewski Pereira, Mariana Alves Resende Salgado, Sayonarah Carvalho Rocha, Hérica L Santos, José Augusto Fp Villar, Ruben G Contreras, Carlos Frederico Leite Fontes, Leandro Augusto Barbosa, Vanessa Faria Cortes
Cisplatin and other platinum-containing drugs have played a crucial role in anticancer treatments for over 30 years. However, treatment with cisplatin may cause serious side effects, such as myelosuppression, nausea, ototoxicity, nephrotoxicity and cell resistance processes. In addition, cardiotonic steroids, particularly digoxin, have recently been suggested to exert potent anticancer effects. Therefore, it is possible that the combined treatment of HeLa cells with cisplatin and digoxin can ameliorate the cytotoxic effects and decrease the side effects of cisplatin...
November 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29125705/m-tuberculosis-mce3c-promotes-mycobacteria-entry-into-macrophages-through-activation-of-%C3%AE-2-integrin-mediated-signaling-pathway
#20
Yong Zhang, Jie Li, Bingxi Li, Jing Wang, Cui Hua Liu
Establishment of infection by facultative intracellular pathogen Mycobacterium tuberculosis (Mtb) requires adherence to and internalization by macrophages. However, the effector molecules exploited by Mtb for entry into macrophages remain to be fully understood. The mammalian cell entry (Mce) proteins play an essential role in facilitating the internalization of mycobacteria into mammalian cells. Here we characterized Mtb Mce3C as a new mycobacterial surface protein that could promote mycobacterial adhesion to and invasion of macrophages in an RGD motif-dependent manner...
November 10, 2017: Cellular Microbiology
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