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mtor protein, human

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https://www.readbyqxmd.com/read/28318036/autophagy-determines-efficiency-of-liver-directed-gene-therapy-with-adeno-associated-viral-vectors
#1
Marianna Hösel, Anke Huber, Susanne Bohlen, Julie Lucifora, Giuseppe Ronzitti, Francesco Puzzo, Florence Boisgerault, Ulrich T Hacker, Wilhelmus J Kwanten, Nora Klöting, Matthias Blüher, Alexander Gluschko, Michael Schramm, Olaf Utermöhlen, Wilhelm Bloch, Federico Mingozzi, Oleg Krut, Hildegard Büning
Use of Adeno-associated viral (AAV) vectors for liver-directed gene therapy has shown considerable success, particularly in patients with severe hemophilia B. However, the high vector doses required to reach therapeutic levels of transgene expression caused liver inflammation in some patients that selectively destroyed transduced hepatocytes. We hypothesized that such detrimental immune responses can be avoided by enhancing the efficacy of AAV vectors in hepatocytes. Because autophagy is a key liver response to environmental stresses, we characterized the impact of hepatic autophagy on AAV infection...
March 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28317380/systems-biology-reveals-ns4b-cyclophilin-a-interaction-a-new-target-to-inhibit-yfv-replication
#2
Alessandra Vidotto, Ana T S Morais, Milene Rocha Ribeiro, Carolina C Pacca, Ana C B Terzian, Laura H V G Gil, Ronaldo Mohana-Borges, Philippe Gallay, Mauricio L Nogueira
Yellow fever virus (YFV) replication is highly dependent upon host cell factors. YFV NS4B is reported to be involved in viral replication and immune evasion. Here, interactions between NS4B and human proteins were determined using a GST pull-down assay and analyzed using 1- DE and LC-MS/MS. We present a total of 207 proteins confirmed using Scaffold 3 Software. Cyclophilin A (CypA), a protein which has been shown to be necessary for the positive regulation of flavivirus replication, was identified as a possible NS4B partner...
March 20, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28316325/silencing-of-the-small-gtpase-diras3-induces-cellular-senescence-in-human-white-adipose-stromal-progenitor-cells
#3
Asim Ejaz, Monika Mattesich, Werner Zwerschke
Inhibition of Akt-mTOR signaling protects from obesity and extends life span in animals. In the present study, we analyse the impact of the small GTPase, GTP-binding RAS-like 3 (DIRAS3), a recently identified weight-loss target gene, on cellular senescence in adipose stromal/progenitor cells (ASCs) derived from human subcutaneous white adipose tissue (sWAT). We demonstrate that DIRAS3 knock-down (KD) in ASCs induces activation of Akt-mTOR signaling and proliferation arrest. DIRAS3 KD ASCs lose the potential to form colonies and are negative for Ki-67...
March 17, 2017: Aging
https://www.readbyqxmd.com/read/28315323/increased-serotonin-signaling-contributes-to-the-warburg-effect-in-pancreatic-tumor-cells-under-metabolic-stress-and-promotes-growth-of-pancreatic-tumors-in-mice
#4
Shu-Heng Jiang, Jun Li, Fang-Yuan Dong, Jian-Yu Yang, De-Jun Liu, Xiao-Mei Yang, Ya-Hui Wang, Min-Wei Yang, Xue-Liang Fu, Xiao-Xin Zhang, Qing Li, Xiu-Feng Pang, Yan-Miao Huo, Jiao Li, Jun-Feng Zhang, Ho-Young Lee, Su-Jae Lee, Wen-Xin Qin, Jian-Ren Gu, Yong-Wei Sun, Zhi-Gang Zhang
BACKGROUND & AIMS: The desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. METHODS: We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras(G12D/+); Trp53(R172H/+); Pdx1-Cre; (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples...
March 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28288786/p21-activated-kinase-4-regulates-hif-1%C3%AE-translation-in-cancer-cells
#5
Hyunju Kim, Dustin J Woo, So Yeon Kim, Eun Gyeong Yang
The p21-activated kinases (Paks) interact with Rac/Cdc42 GTPases to regulate the actin cytoskeleton as well as various signaling pathways. Although activation of Paks in many human cancers is known to mediate cancer progression, the role of Pak proteins in hypoxia is poorly understood. In this study, we found that both Pak1 and Pak4 are highly expressed in HeLa cervical cancer cells, but only Pak4 knockdown attenuates expression of hypoxia-inducible factor-1α (HIF-1α) in hypoxia. We further discovered that Pak4 regulates HIF-1α translation via the Akt-mTOR-4E-BP1 pathway under hypoxic conditions...
March 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28284560/computational-discovery-of-niclosamide-ethanolamine-a-repurposed-drug-candidate-that-reduces-growth-of-hepatocellular-carcinoma-cells-in-vitro-and-in-mice-by-inhibiting-cdc37-signaling
#6
Bin Chen, Wei Wei, Li Ma, Bin Yang, Ryan M Gill, Mei-Sze Chua, Atul J Butte, Samuel So
BACKGROUND & AIMS: Drug repositioning offers a shorter approval process than new drug development. We therefore searched large public datasets of drug-induced gene expression signatures to identify agents that might be effective against hepatocellular carcinoma (HCC). METHODS: We searched public databases of mRNA expression patterns reported from HCC specimens from patients, HCC cell lines, and cells exposed to various drugs. We identified drugs that might specifically increase expression of genes that are downregulated in HCCs and reduce expression of genes upregulated in HCCs using a non-parametric, rank-based pattern-matching strategy based on the Kolmogorov-Smirnov statistic...
March 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28283069/mtor-signaling-in-growth-metabolism-and-disease
#7
REVIEW
Robert A Saxton, David M Sabatini
The mechanistic target of rapamycin (mTOR) coordinates eukaryotic cell growth and metabolism with environmental inputs, including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in regulating many fundamental cell processes, from protein synthesis to autophagy, and deregulated mTOR signaling is implicated in the progression of cancer and diabetes, as well as the aging process. Here, we review recent advances in our understanding of mTOR function, regulation, and importance in mammalian physiology...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28282611/phase-ib-dose-finding-study-of-abiraterone-acetate-plus-buparlisib-bkm120-or-dactolisib-bez235-in-patients-with-castration-resistant-prostate-cancer
#8
Christophe Massard, Kim Nguyen Chi, Daniel Castellano, Johann de Bono, Gwenaelle Gravis, Luc Dirix, Jean-Pascal Machiels, Alain Mita, Begona Mellado Gonzalez, Sabine Turri, Joan Maier, Denes Csonka, Arunava Chakravartty, Karim Fizazi
BACKGROUND: The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signalling axis and androgen receptor (AR) pathways exhibit reciprocal feedback regulation in phosphatase and tensin homologue (PTEN)-deficient metastatic castration-resistant prostate cancer (CRPC) in preclinical models. This phase Ib study evaluated the pan-PI3K inhibitor buparlisib (BKM120) and the dual pan-PI3K/ mammalian target of rapamycin (mTOR) inhibitor dactolisib (BEZ235) in combination with abiraterone acetate (AA) in patients with CRPC...
March 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28281969/cstb-downregulation-promotes-cell-proliferation-and-migration-and-suppresses-apoptosis-in-gastric-cancer-sgc-7901-cell-line
#9
Jian Zhang, ZhenFeng Shi, JinXing Huang, XiaoGuang Zou
This study aimed to investigate the pivotal role of cystatin B (CSTB) in the development of gastric cancer and to explore its possible regulatory mechanism. Human gastric cancer SGC-7901 cells as a model in vitro were transfected with plasmid PCDNA3.1-CSTB and siRNA-CSTB using Lipofectamine 2000. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to determine the relative expression of CSTB and PI3K/Akt/mTOR pathway-related protein. Moreover, MTT assay, Transwell assay, and flow cytometry were used to assess cell proliferation, migration, and apoptosis, respectively...
October 27, 2016: Oncology Research
https://www.readbyqxmd.com/read/28273117/activation-of-odorant-receptor-in-colorectal-cancer-cells-leads-to-inhibition-of-cell-proliferation-and-apoptosis
#10
Lea Weber, Klaudia Al-Refae, Juliane Ebbert, Peter Jägers, Janine Altmüller, Christian Becker, Stephan Hahn, Günter Gisselmann, Hanns Hatt
The analysis and functional characterization of ectopically expressed human olfactory receptors (ORs) is becoming increasingly important, as many ORs have been identified in several healthy and cancerous tissues. OR activation has been demonstrated to have influence on cancer cell growth and progression. Here, ORs were identified using RNA-Seq analyses and RT-PCR. We demonstrated the OR protein localization in HCT116 cells using immunocytochemistry (IHC). In order to analyze the physiological role of OR51B4, we deorphanized the receptor by the use of CRE-Luciferase assays, conducted calcium imaging experiments as well as scratch- and proliferation assays...
2017: PloS One
https://www.readbyqxmd.com/read/28272965/regulation-of-4e-bp1-activity-in-the-mammalian-oocyte
#11
Denisa Jansova, Marketa Koncicka, Anna Tetkova, Renata Cerna, Radek Malik, Edgar Del Llano, Michal Kubelka, Andrej Susor
Fully grown mammalian oocytes utilize transcripts synthetized and stored during earlier development. RNA localization followed by a local translation is a mechanism responsible for the regulation of spatial and temporal gene expression. Here we show that the mouse oocyte contains three forms of cap-dependent translational repressor expressed on the mRNA level: 4E-BP1, 4E-BP2 and 4E-BP3. However, only 4E-BP1 is present as a protein in oocytes, it becomes inactivated by phosphorylation after nuclear envelope breakdown and as such it promotes cap-dependent translation after NEBD...
March 8, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28266023/astragaloside-ii-sensitizes-human-hepatocellular-carcinoma-cells-to-5-fluorouracil-via-suppression-of-autophagy
#12
Meng Wang, Can Huang, Yong Su, Cui Yang, Quan Xia, Du-Juan Xu
OBJECTIVES: Inhibition of autophagy has been increasingly recognized as a potential therapeutic approach against cancer. Our previous reports showed that Astragaloside II improves hepatic cancer cells resistance by downregulating MDR1 and P-gp .The purpose of this study was to further investigated the effect of autophagy on AS-II reversing multidrug resistance and its molecular mechanism in hepatocellular carcinoma cells in vitro. METHODS: Bel-7402 and Bel-7402/FU cell lines were used in this study...
March 7, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28264931/key-proteins-and-pathways-that-regulate-lifespan
#13
Haihui Pan, Toren Finkel
Here, we review three sets of key proteins and their corresponding downstream pathways that have been linked to extending lifespan and promoting health span in a wide range of organisms. In particular, we review the biology of the sirtuin family of proteins, the Insulin/Insulin-like Growth Factor (IGF) signaling (IIS) pathway, and the mechanistic Target of Rapamycin (mTOR). Using insights derived from simple model organisms, mice and humans we discuss how these proteins and pathways may potentially alter the rate of aging...
March 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28260058/apigenin-inhibits-proliferation-and-invasion-and-induces-apoptosis-and-cell-cycle-arrest-in-human-melanoma-cells
#14
Guangming Zhao, Xiaodong Han, Wei Cheng, Jing Ni, Yunfei Zhang, Jingrong Lin, Zhiqi Song
Malignant melanoma is the most invasive and fatal form of cutaneous cancer. Moreover it is extremely resistant to conventional chemotherapy and radiotherapy. Apigenin, a non-mutagenic flavonoid, has been found to exhibit chemopreventive and/or anticancerogenic properties in many different types of human cancer cells. Therefore, apigenin may have particular relevance for development as a chemotherapeutic agent for cancer treatment. In the present study, we investigated the effects of apigenin on the viability, migration and invasion potential, dendrite morphology, cell cycle distribution, apoptosis, phosphorylation of the extracellular signal-regulated protein kinase (ERK) and the AKT/mTOR signaling pathway in human melanoma A375 and C8161 cell lines in vitro...
February 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28249781/assessment-of-anti-cancerous-potential-of-6-gingerol-tongling-white-ginger-and-its-synergy-with-drugs-on-human-cervical-adenocarcinoma-cells
#15
Fang Zhang, Jian-Guo Zhang, Jie Qu, Qi Zhang, Chandan Prasad, Zhao-Jun Wei
The anti-cancerous activity of 6-gingerol extracted from Tongling White Ginger was investigated. 6-Gingerol inhibited the growth of HeLa cells with IC50 (96.32 μM) and IC80 (133.01 μM) and led to morphological changes, induced the cell cycle arrest in G0/G1-phase and ultimately resulted into apoptosis. Among cell cycle-related genes and proteins, the expression of cyclin (A, D1, E1) reduced, while of CDK-1, p21 and p27 showed slight decrease, except cyclin B1 and E1 (protein). Western blotting reported the induction of apoptosis with an increased Bax/Bcl-2 ratio, release of cytochrome c, cleavage of caspase-3, -8, -9 and PRPP in treated cells...
February 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28249041/a-dangerous-liaison-leptin-and-spla2-iia-join-forces-to-induce-proliferation-and-migration-of-astrocytoma-cells
#16
Rubén Martín, Claudia Cordova, Beatriz Gutiérrez, Marita Hernández, María L Nieto
Glioblastoma, the most aggressive type of primary brain tumour, shows worse prognosis linked to diabetes or obesity persistence. These pathologies are chronic inflammatory conditions characterized by altered profiles of inflammatory mediators, including leptin and secreted phospholipase A2-IIA (sPLA2-IIA). Both proteins, in turn, display diverse pro-cancer properties in different cell types, including astrocytes. Herein, to understand the underlying relationship between obesity and brain tumors, we investigated the effect of leptin, alone or in combination with sPLA2-IIA on astrocytoma cell functions...
2017: PloS One
https://www.readbyqxmd.com/read/28247968/breaking-up-and-making-up-the-secret-life-of-the-vacuolar-h-atpase
#17
REVIEW
Rebecca A Oot, Sergio Couoh-Cardel, Stuti Sharma, Nicholas J Stam, Stephan Wilkens
The vacuolar ATPase (V-ATPase; V1 Vo -ATPase) is a large multisubunit proton pump found in the endomembrane system of all eukaryotic cells where it acidifies the lumen of subcellular organelles including lysosomes, endosomes, the Golgi apparatus and clathrin coated vesicles. V-ATPase function is essential for pH and ion homeostasis, protein trafficking, endocytosis, mechanistic target of rapamycin (mTOR) and Notch signaling, as well as hormone secretion and neurotransmitter release. V-ATPase can also be found in the plasma membrane of polarized animal cells where its proton pumping function is involved in bone remodeling, urine acidification and sperm maturation...
March 1, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28245561/negative-regulators-of-jak-stat-signaling-in-rheumatoid-arthritis-and-osteoarthritis
#18
REVIEW
Charles J Malemud
Elevated levels of pro-inflammatory cytokines are generally thought to be responsible for driving the progression of synovial joint inflammation in rheumatoid arthritis (RA) and osteoarthritis (OA). These cytokines activate several signal transduction pathways, including the Janus kinase/Signal Transducers and Activators of Transcription (JAK/STAT), Stress-Activated/Mitogen-Activated Protein Kinase (SAPK/MAPK) and phosphatidylinositol-3-kinase/Akt/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathways which regulate numerous cellular responses...
February 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28243617/data-supporting-the-inability-of-indomethacin-to-induce-autophagy-in-u251-glioma-cells
#19
Aleksandar Pantovic, Katarina Arsikin, Milica Kosic, Biljana Ristic, Vladimir Trajkovic, Ljubica Harhaji-Trajkovic
Autophagy, a catabolic process involving intracellular degradation of unnecessary or dysfunctional cellular components through the lysosomal machinery, could act as a prosurvival, as well as a cytotoxic mechanism (Parzych and Klionsky, 2014) [1]. Cyclooxygenase inhibitor indomethacin inhibits proliferation of glioma cells, and has been reported to reduce the activity of the main autophagy repressor mammalian target of rapamycin (mTOR) (Pantovic et al., 2016) [2]. Here we investigated the ability of indomethacin to induce autophagy in U251 human glioma cells...
April 2017: Data in Brief
https://www.readbyqxmd.com/read/28243322/targeting-metabolic-remodeling-in-triple-negative-breast-cancer-in-a-murine-model
#20
Verónica García-Castillo, Eduardo López-Urrutia, Octavio Villanueva-Sánchez, Miguel Á Ávila-Rodríguez, Alejandro Zentella-Dehesa, Carlo Cortés-González, César López-Camarillo, Nadia J Jacobo-Herrera, Carlos Pérez-Plasencia
Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis...
2017: Journal of Cancer
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