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mtor protein, human

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https://www.readbyqxmd.com/read/28223541/targeting-growth-hormone-receptor-in-human-melanoma-cells-attenuates-tumor-progression-and-epithelial-mesenchymal-transition-via-suppression-of-multiple-oncogenic-pathways
#1
Reetobrata Basu, Shiyong Wu, John J Kopchick
Recent reports have confirmed highest levels of growth hormone (GH) receptor (GHR) transcripts in melanoma, one of the most aggressive forms of human cancer. Yet the mechanism of GH action in melanoma remains mostly unknown. Here, using human malignant melanoma cells, we examined the effects of GH excess or siRNA mediated GHR knock-down (GHRKD) on tumor proliferation, migration and invasion. GH promoted melanoma progression while GHRKD attenuated the same. Western blot analysis revealed drastic modulation of multiple oncogenic signaling pathways (JAK2, STAT1, STAT3, STAT5, AKT, mTOR, SRC and ERK1/2) following addition of GH or GHRKD...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28222438/microrna-29b-inhibits-angiogenesis-by-targeting-vegfa-through-the-mapk-erk-and-pi3k-akt-signaling-pathways-in-endometrial-carcinoma
#2
Hong-Xia Chen, Xiao-Xia Xu, Bu-Zhen Tan, Zhi Zhang, Xiao-Dong Zhou
OBJECTIVE: The purpose of this study is to explore the effects of microRNA-29b (miR-29b) regulating MAPK/ERK and PI3K/Akt signaling pathways on angiogenesis in endometrial carcinoma (EC) by targeting VEGFA. METHODS: Between February 2013 and April 2015, 126 EC patients admitted to the Second Affiliated Hospital of Nanchang University were randomly selected, with 126 EC tissues and the corresponding adjacent normal tissues collected after surgery. The human EC cell lines RL-95-2 and HEC-1-B and human endometrial cells were assigned to the normal group (human endometrial cells), the blank group (untransfected RL-95-2 or HEC-1-B cells), the pMIR-control group (RL-95-2 or HEC-1-B cells transfected with an empty vector), the pMIR-miR-29b group (RL-95-2 or HEC-1-B cells transfected with the miR-29b plasmid), LNA-control group (RL-95-2 or HEC-1-B cells transfected with an oligonucleotide inhibitors control), the LNA-miR-29b inhibitors group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors), the LNA-miR-29b inhibitors + PD98059 group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and PD98059, an inhibitor of the MAPK/ERK signaling pathway) and the LNA-miR-29b inhibitors + wortmannin group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and wortmannin, an inhibitor of the PI3K/Akt signaling pathway)...
February 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28218386/glucose-adsorption-to-chitosan-membranes-increases-proliferation-of-human-chondrocyte-via-mammalian-target-of-rapamycin-complex-1-and-sterol-regulatory-element-binding-protein-1-signaling
#3
Shun-Fu Chang, Kuo-Chin Huang, Chin-Chang Cheng, Yu-Ping Su, Ko-Chao Lee, Cheng-Nan Chen, Hsin-I Chang
BACKGROUND: Osteoarthritis (OA) is currently still an irreversible degenerative disease of the articular cartilage. Recent, dextrose (D-glucose) intraarticular injection prolotherapy for OA patients has been reported to benefit the chondrogenic stimulation of damaged cartilage. However, the detailed mechanism of glucose's effect on cartilage repair remains unclear. Chitosan, a naturally derived polysaccharide, has recently been investigated as a surgical or dental dressing to control breeding...
February 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28212891/sulforaphane-inhibits-platelet-derived-growth-factor-induced-vascular-smooth-muscle-cell-proliferation-by-targeting-mtor-p70s6kinase-signaling-independent-of-nrf2-activation
#4
Noha M Shawky, Lakshman Segar
Activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor) and/or inhibition of mammalian target of rapamycin (mTOR) are implicated in the suppression of vascular smooth muscle cell (VSMC) proliferation. The present study has examined the likely regulatory effects of sulforaphane (SFN, an antioxidant) on Nrf2 activation and platelet-derived growth factor (PDGF)-induced mTOR signaling in VSMCs. Using human aortic VSMCs, nuclear extraction and siRNA-mediated downregulation studies were performed to determine the role of Nrf2 on SFN regulation of PDGF-induced proliferative signaling...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28205653/phosphorylation-of-zinc-channel-zip7-drives-mapk-pi3k-and-mtor-growth-and-proliferation-signalling
#5
T Nimmanon, S Ziliotto, S Morris, L Flanagan, K M Taylor
Zinc is an essential trace element participating in diverse biological processes. Cellular zinc levels are strictly controlled by two families of transport proteins: ZIP channels (SLC39A) and ZnT transporters (SLC30A). ZIP channels increase cytosolic zinc levels by importing zinc into cells or releasing zinc from intracellular stores such as the ER. Among all the 14 human members of the ZIP family, ZIP7 is a gatekeeper of zinc release from intracellular stores, requiring post-translational activation by phosphorylation on residues S275 and S276, resulting in activation of multiple downstream pathways...
February 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28197628/resveratrol-induced-autophagy-and-apoptosis-in-cisplatin-resistant-human-oral-cancer-car-cells-a-key-role-of-ampk-and-akt-mtor-signaling
#6
Chao-Hsiang Chang, Chao-Ying Lee, Chi-Cheng Lu, Fuu-Jen Tsai, Yuan-Man Hsu, Je-Wei Tsao, Yu-Ning Juan, Hong-Yi Chiu, Jai-Sing Yang, Ching-Chiung Wang
Resveratrol is known to be an effective chemo-preventive phytochemical against multiple tumor cells. However, the increasing drug resistance avoids the cancer treatment in oral cavity cancer. In this study, we investigated the oral antitumor activity of resveratrol and its mechanism in cisplatin-resistant human oral cancer CAR cells. Our results demonstrated that resveratrol had an extremely low toxicity in normal oral cells and provoked autophagic cell death to form acidic vesicular organelles (AVOs) and autophagic vacuoles in CAR cells by acridine orange (AO) and monodansylcadaverine (MDC) staining...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28186992/autophagy-is-highly-targeted-among-host-comparative-proteomes-during-infection-with-different-virulent-rabv-strains
#7
Ling Li, Hongli Jin, Hualei Wang, Zengguo Cao, Na Feng, Jianzhong Wang, Yongkun Zhao, Xuexing Zheng, Pengfei Hou, Nan Li, Hang Chi, Pei Huang, Cuicui Jiao, Qian Li, Lina Wang, Tiecheng Wang, Weiyang Sun, Yuwei Gao, Changchun Tu, Guixue Hu, Songtao Yang, Xianzhu Xia
Rabies virus (RABV) is a neurotropic virus that causes serious disease in humans and animals worldwide. It has been reported that different RABV strains can result in divergent prognoses in animal model. To identify host factors that affect different infection processes, a kinetic analysis of host proteome alterations in mouse brains infected with different virulent RABV strains was performed using isobaric tags for a relative and absolute quantification (iTRAQ)-liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach, and this analysis identified 147 differentially expressed proteins (DEPs) between the pathogenic challenge virus standard (CVS)-11 strain and the attenuated SRV9 strain...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28183860/diminished-satellite-cell-fusion-and-s6k1-expression-in-myotubes-derived-from-skeletal-muscle-of-low-birth-weight-neonatal-pigs
#8
Ying Chen, Haibo Zhu, Sydney R McCauley, Lidan Zhao, Sally E Johnson, Robert P Rhoads, Samer W El-Kadi
Low birth weight (LBWT) is consistently associated with impaired postnatal muscle growth in mammals. Satellite cell (SC)-mediated myonuclear incorporation precedes protein accumulation in the early stages of postnatal muscle development and growth. The objective of this study was to investigate proliferation and differentiation of SCs and the regulation of protein synthesis signaling in response to insulin-like growth factor (IGF)-I stimulation in SC-derived myotubes of LBWT neonatal pigs. SCs isolated from Longissimus dorsi muscle of LBWT and NBWT pigs (3-d-old, n = 8) were cultured and induced to proliferate and differentiate to myotubes in vitro...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28179320/detection-of-somatic-mutations-in-gastroenteropancreatic-neuroendocrine-tumors-using-targeted-deep-sequencing
#9
Samuel Backman, Olov Norlén, Barbro Eriksson, Britt Skogseid, Peter Stålberg, Joakim Crona
: Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28165663/interrogating-the-hidden-phosphoproteome
#10
Un-Beom Kang, William M Alexander, Jarrod A Marto
Post-genomic studies continue to highlight the potential clinical importance of protein phosphorylation signaling pathways in drug discovery. Unfortunately the dynamic range and variable stoichiometry of protein phosphorylation continues to stymie efforts to achieve comprehensive characterization of the human phosphoproteome. In this study, we develop a complementary, two-stage method for enrichment of cysteine-containing phosphopeptides combined with TMT multiplex labeling for relative quantification. Use of this approach with multi-dimension fractionation in mammalian cells yielded more than 7,000 unique cys-phosphopeptide sequences, comprising 15%-20% novel phosphorylation sites...
February 6, 2017: Proteomics
https://www.readbyqxmd.com/read/28165150/everolimus-inhibits-growth-of-gemcitabine-resistant-pancreatic-cancer-cells-via-induction-of-caspase-dependent-apoptosis-and-g2-m-arrest
#11
Tao Peng, Q Ping Dou
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. While Gemcitabine-based chemotherapy is the first-line treatment for locally advanced pancreatic cancer, its resistance is a large obstacle in the field. Understanding the molecular basis of gemcitabine resistance is therefore critical for increasing the efficacy of gemcitabine-based chemotherapy and improving the survival rate of the cancer patients. Here, we investigated the sensitivity of a pair of established human pancreatic cancer cell lines, MIAPaCa-E (relatively sensitive to gemcitabine, called GS) and MIAPaCa-M (highly resistant to gemcitabine, called GR) to various inhibitors of EGFR or PI3K/AKT/mTOR pathways...
February 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28154014/a-tumor-cell-selective-inhibitor-of-mitogen-activated-protein-kinase-phosphatases-sensitizes-breast-cancer-cells-to-lymphokine-activated-killer-cell-activity
#12
Christof T Kaltenmeier, Laura L Vollmer, Lawrence A Vernetti, Lindsay Caprio, Keanu Davis, Vasiliy N Korotchenko, Billy W Day, Michael Tsang, Keren I Hulkower, Michael T Lotze, Andreas Vogt
Dual specificity mitogen activated protein kinase (MAPK) phosphatases (DUSP-MKPs) have been hypothesized to maintain cancer cell survival by buffering excessive MAPK signaling caused by upstream activating oncogenic products. A large and diverse body of literature suggests that genetic depletion of DUSP-MKPs can reduce tumorigenicity, suggesting that hyperactivating MAPK signaling by DUSP-MKP inhibitors could be a novel strategy to selectively affect the transformed phenotype. Through in vivo structure activity relationship studies in transgenic zebrafish we recently identified a hyperactivator of Fibroblast Growth Factor signaling (BCI-215) that is devoid of developmental toxicity and restores defective MAPK activity caused by overexpression of DUSP1 and DUSP6 in mammalian cells...
February 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28153010/targeting-muc1-c-inhibits-the-akt-s6k1-elf4a-pathway-regulating-tigar-translation-in-colorectal-cancer
#13
Rehan Ahmad, Maroof Alam, Masanori Hasegawa, Yasumitsu Uchida, Omar Al-Obaid, Surender Kharbanda, Donald Kufe
BACKGROUND: Colorectal cancer is third most common malignancy and is the second most common cause of cancer-related death. The MUC1 heterodimeric protein is aberrantly overexpressed in colorectal cancer and has been linked to poor outcomes in this disease. Here, we investigate the effects of the MUC1-C subunit inhibitor (GO-203), which disrupts MUC1-C homo-oligomerization, on human colorectal cancer cells. METHODS: TIGAR mRNA level was determined using qRT-PCR. Western blotting was used to measure TIGAR protein level and AKT-mTOR-S6K1 pathways...
February 2, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28152510/akt-mtor-mediated-induction-of-bystander-effect-signaling-in-a-nucleus-independent-manner-in-irradiated-human-lung-adenocarcinoma-epithelial-cells
#14
Lu Li, Lu Wang, Kevin M Prise, K N Yu, Guodong Chen, Lianyun Chen, Yide Mei, Wei Han
Cytoplasm is an important target for the radiation-induced bystander effect (RIBE). In the present work, the critical role of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in the generation of RIBE signaling after X-ray irradiation and the rapid phosphorylation of Akt and mTOR was observed in the cytoplasm of irradiated human lung adenocarcinoma epithelial (A549) cells. Targeting A549 cytoplasts with individual protons from a microbeam showed that RIBE signal(s) mediated by the Akt/mTOR pathway were generated even in the absence of a cell nucleus...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28148781/the-amino-acid-metabolite-homocysteine-activates-mtorc1-to-inhibit-autophagy-and-form-abnormal-proteins-in-human-neurons-and-mice
#15
Khoosheh Khayati, Henri Antikainen, Edward M Bonder, Gregory F Weber, Warren D Kruger, Hieronim Jakubowski, Radek Dobrowolski
The molecular mechanisms leading to and responsible for age-related, sporadic Alzheimer's disease (AD) remain largely unknown. It is well documented that aging patients with elevated levels of the amino acid metabolite homocysteine (Hcy) are at high risk of developing AD. We investigated the impact of Hcy on molecular clearance pathways in mammalian cells, including in vitro cultured induced pluripotent stem cell-derived forebrain neurons and in vivo neurons in mouse brains. Exposure to Hcy resulted in up-regulation of the mechanistic target of rapamycin complex 1 (mTORC1) activity, one of the major kinases in cells that is tightly linked to anabolic and catabolic pathways...
February 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28143872/musashi-rna-binding-proteins-as-cancer-drivers-and-novel-therapeutic-targets
#16
Alexander E Kudinov, John Karanicolas, Erica A Golemis, Yanis Boumber
Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. While much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act post-transcriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBPs) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance...
January 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#17
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/28132115/rictor-expression-in-esophageal-squamous-cell-carcinoma-and-its-clinical-significance
#18
Wei-Jia Jiang, Ru-Xue Feng, Jia-Tao Liu, Lu-Lu Fan, Hua Wang, Guo-Ping Sun
Esophageal cancer is one of the most common malignant tumors in the world, and its incidence is the eighth highest; meanwhile, its fatality rate is the sixth highest. The PI3K/Akt/mTOR signaling pathway plays a required role in human cancer, including cell survival, metabolism and migration. As a kind of important scaffold protein in mTORC2, RICTOR has showed over-expression in several malignancies like melanoma and endometrial cancer. In this research, we selected 201 cases of paraffin specimens from patients diagnosed as esophageal squamous cell carcinoma after surgical treatment and then estimated the RICTOR expression in each esophageal squamous cell carcinoma tissue by using the immunohistochemical streptavidin-peroxidase technique...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28131727/long-term-protective-effects-of-aav9-mesencephalic-astrocyte-derived-neurotrophic-factor-gene-transfer-in-parkinsonian-rats
#19
Fei Hao, Chun Yang, Sha-Sha Chen, Yan-Yan Wang, Wei Zhou, Qiang Hao, Tao Lu, Barry Hoffer, Li-Ru Zhao, Wei-Ming Duan, Qun-Yuan Xu
Intrastriatal injection of mesencephalic astrocyte-derived neurotrophic factor (MANF) protein has been shown to provide neuroprotective and neurorestorative effects in a 6-hydroxydopamine (6-OHDA) - lesioned rat model of Parkinson's disease. Here, we used an adeno-associated virus serotype 9 (AAV9) vector to deliver the human MANF (hMANF) gene into the rat striatum 10days after a 6-OHDA lesion to examine long-term effects of hMANF on nigral dopaminergic neurons and mechanisms underlying MANF neuroprotection...
January 25, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28127425/novel-metabolic-and-physiological-functions-of-branched-chain-amino-acids-a-review
#20
REVIEW
Shihai Zhang, Xiangfang Zeng, Man Ren, Xiangbing Mao, Shiyan Qiao
It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including: (1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis...
2017: Journal of Animal Science and Biotechnology
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