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mtor protein, human

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https://www.readbyqxmd.com/read/29214525/treatment-of-melanoma-with-selected-inhibitors-of-signaling-kinases-effectively-reduces-proliferation-and-induces-expression-of-cell-cycle-inhibitors
#1
Dorota Ciołczyk-Wierzbicka, Dorota Gil, Piotr Laidler
Cancer treatment often tends to involve direct targeting enzymes essential for the growth and proliferation of cancer cells. The aim of this study was the recognition of the possible role of selected protein kinases: PI3K, ERK1/2, and mTOR in cell proliferation and cell cycle in malignant melanoma. We investigated the role of protein kinase inhibitors: U0126 (ERK1/2), LY294002 (PI3K), rapamycin (mTOR), everolimus (mTOR), GDC-0879 (B-RAF), and CHIR-99021 (GSK3beta) in cell proliferation and expression of crucial regulatory cell cycle proteins in human melanoma cells: WM793 (VGP) and Lu1205 (metastatic)...
December 6, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29212935/tetraspanin-cd63-bridges-autophagic-and-endosomal-processes-to-regulate-exosomal-secretion-and-intracellular-signaling-of-epstein-barr-virus-lmp1
#2
Stephanie N Hurwitz, Mujeeb R Cheerathodi, Dingani Nkosi, Sara B York, David G Meckes
The tetraspanin protein CD63 has been recently described as a key factor in extracellular vesicle (EV) production and endosomal cargo sorting. In the context of Epstein-Barr virus (EBV) infection, CD63 is required for the efficient packaging of the major viral oncoprotein latent membrane protein 1 (LMP1) into exosomes and other EV populations, and acts as a negative regulator of LMP1 intracellular signaling. Accumulating evidence has also pointed to intersections of the endosomal and autophagy pathways in maintaining cellular secretory processes, and as sites for viral assembly and replication...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29212182/oncogenic-p95her2-611ctf-primes-human-breast-epithelial-cells-for-metabolic-stress-induced-down-regulation-of-flip-and-activation-of-trail-r-caspase-8-dependent-apoptosis
#3
Rosa Martín-Pérez, Rosario Yerbes, Rocío Mora-Molina, Ana Cano-González, Joaquín Arribas, Massimiliano Mazzone, Abelardo López-Rivas, Carmen Palacios
Oncogenic transformation triggers reprogramming of cell metabolism, as part of the tumorigenic process. However, metabolic reprogramming may also increase the sensitivity of transformed cells to microenvironmental stress, at the early stages of tumor development. Herein, we show that transformation of human breast epithelial cells by the p95HER2/611CTF oncogene markedly sensitizes these cells to metabolic stress induced by the simultaneous inhibition of glucose and glutamine metabolism. In p95HER2/611CTF-transformed cells, metabolic stress activates a TNF related apoptosis-inducing ligand (TRAIL)-R and caspase-8-dependent apoptotic process that requires prior down-regulation of cellular FLICE-like inhibitor protein (c-FLIP) levels...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29208365/targeting-pi3k-mtor-erk-and-bcl-2-signaling-network-shows-superior-antileukemic-activity-against-aml-ex-vivo
#4
Yongwei Su, Xinyu Li, Jun Ma, Jianyun Zhao, Shuang Liu, Guan Wang, Holly Edwards, Jeffrey W Taub, Hai Lin, Yubin Ge
Acute myeloid leukemia (AML) remains challenging to treat and needs more effective treatments. The PI3K/mTOR pathway is involved in cell survival and has been shown to be constitutively active in 50-80% of AML patients. However, targeting the PI3K/mTOR pathway results in activation of the ERK pathway, which also plays an important role in cell survival. In addition, AML cells often overexpress antiapoptotic Bcl-2 family proteins (e.g., Bcl-2), preventing cell death. Thus, our strategy here is to target the PI3K, mTOR (by VS-5584, a PI3K and mTOR dual inhibitor), ERK (by SCH772984, an ERK-selective inhibitor), and Bcl-2 (by ABT-199, a Bcl-2-selective inhibitor) signaling network to kill AML cells...
December 2, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29208325/inhibitory-effects-of-compound-dmbt-on-hypoxia-induced-vasculogenic-mimicry-in-human-breast-cancer
#5
Shuixian Li, Qianyun Zhang, Lichun Zhou, Yanhui Guan, Shang Chen, Yu Zhang, Xiuzhen Han
Breast cancer is one of the most serious malignant tumors that harm to women's health. Vasculogenic mimicry (VM) is an alternative type of blood supplement independent of endothelial vessels, which refers to the formation of tumor cell-lined vessels and is associated with tumor invasion, metastasis and poor cancer patient prognosis. Prior antiangiogenic therapy just focused on vascular endothelial cells and did not significantly affect VM. DMBT, 6, 6'-bis (2, 3-dimethoxybenzoyl)-a, a-D-trehalose, has shown to have multiple anti-tumor invasion and metastasis activities; however the exact mechanism is not thoroughly elucidated...
December 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29204055/combined-treatment-of-pancreatic-cancer-xenograft-with-90y-itga6b4-mediated-radioimmunotherapy-and-pi3k-mtor-inhibitor
#6
Winn Aung, Atsushi B Tsuji, Hitomi Sudo, Aya Sugyo, Yoshinori Ukai, Katsushi Kouda, Yoshikazu Kurosawa, Takako Furukawa, Tsuneo Saga, Tatsuya Higashi
AIM: To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy (RIT) and PI3K/mTOR inhibitor BEZ235 in a pancreatic cancer model. METHODS: Phosphorylation of Akt, mTOR, the downstream effectors eukaryotic initiation factor 4E binding protein 1 (4EBP1) and S6 ribosomal protein (S6) were evaluated in BxPC-3 human pancreatic cancer cells treated with Yttrium-90 (90Y) labeled anti-integrin α6β4 antibody (ITGA6B4) and BEZ235 by western blotting...
November 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29203232/thioredoxin-interacting-protein-deficiency-ameliorates-diabetic-retinal-angiogenesis
#7
Jialiang Duan, Chunyang Du, Yonghong Shi, Danyan Liu, Jingxue Ma
Diabetic retinopathy is the leading cause of blindness among working-aged adults around the world. Hyperglycemia and intraocular vascular endothelial growth factor (VEGF) over-accumulation are essential for the progression of diabetic retinopathy, which eventually results in proliferative diabetic retinopathy, characterized by pathologic angiogenesis and impaired vision. Thioredoxin-interacting protein (TXNIP) was highly induced in retinal endothelial cells under diabetic conditions. However, the role of TXNIP in diabetes-associated retinal angiogenesis remains elusive...
December 1, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29201217/curcumin-inhibits-the-development-of-non-small-cell-lung-cancer-by-inhibiting-autophagy-and-apoptosis
#8
Aili Wang, Jinxiang Wang, Shuming Zhang, Hongxia Zhang, Zhenyang Xu, Xiaohui Li
Among patients with primary lung cancer, 75-80% present with non-small cell lung cancer (NSCLC). However, there is a lack of studies into the potential preventive effects of curcumin against the activation of autophagy in NSCLC. Therefore, the present study primarily focused on the protective role of curcumin in NSCLC. It was demonstrated that curcumin decreased the viability of the human lung cancer cells lines, A549 and H1299, in a time-and dose-dependent manner (P<0.05). Treatment with curcumin also suppressed the colony formation capacities of A549 and H1299 cells...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29196555/ral-gtpases-biology-and-potential-as-therapeutic-targets-in-cancer
#9
REVIEW
Chao Yan, Dan Theodorescu
More than a hundred proteins comprise the RAS superfamily of small GTPases. This family can be divided into RAS, RHO, RAB, RAN, ARF, and RAD subfamilies, with each shown to play distinct roles in human cells in both health and disease. The RAS subfamily has a well-established role in human cancer with the three genes, HRAS, KRAS, and NRAS being the commonly mutated in tumors. These RAS mutations, most often functionally activating, are especially common in pancreatic, lung, and colorectal cancers. Efforts to inhibit RAS and related GTPases have produced inhibitors targeting the downstream effectors of RAS signaling, including inhibitors of the RAF-mitogen-activated protein kinase/extracellular signal-related kinase (ERK)-ERK kinase pathway and the phosphoinositide-3-kinase-AKT-mTOR kinase pathway...
January 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29187895/follicular-stimulating-hormone-accelerates-atherogenesis-by-increasing-endothelial-vcam-1-expression
#10
Xiaosa Li, Weiyu Chen, Ping Li, Jinzhi Wei, Yang Cheng, Pei Liu, Qing Yan, Xingyan Xu, Yuhong Cui, Zhengtian Gu, Tommaso Simoncini, Xiaodong Fu
Rationale: Postmenopausal atherosclerosis (AS) has for decades been attributed to estrogen deficiency. Although the follicular stimulating hormone (FSH) levels rise sharply in parallel, the direct effect of FSH on AS has never been investigated. In this study, we explored the possible role of FSH in the development of AS. Methods: This was a prospective cohort study of 48 healthy premenopausal and 15 postmenopausal women. ApoE knockout mice were used as atherosclerosis model and human umbilical vascular endothelial cells (HUVECs) were cultured as cell model...
2017: Theranostics
https://www.readbyqxmd.com/read/29180720/snx27-links-dgk%C3%AE-to-the-control-of-transcriptional-and-metabolic-programs-in-t-lymphocytes
#11
M Tello-Lafoz, C Rodríguez-Rodríguez, G Kinna, L S Loo, W Hong, B M Collins, R D Teasdale, I Mérida
Sorting nexin 27 (SNX27) recycles PSD-95, Dlg1, ZO-1 (PDZ) domain-interacting membrane proteins and is essential to sustain adequate brain functions. Here we define a fundamental SNX27 function in T lymphocytes controlling antigen-induced transcriptional activation and metabolic reprogramming. SNX27 limits the activation of diacylglycerol (DAG)-based signals through its high affinity PDZ-interacting cargo DAG kinase ζ (DGKζ). SNX27 silencing in human T cells enhanced T cell receptor (TCR)-stimulated activator protein 1 (AP-1)- and nuclear factor κB (NF-κB)-mediated transcription...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29179453/microrna-deregulation-in-nonalcoholic-steatohepatitis-associated-liver-carcinogenesis
#12
Aline de Conti, Juliana Festa Ortega, Volodymyr Tryndyak, Kostiantyn Dreval, Fernando Salvador Moreno, Ivan Rusyn, Frederick A Beland, Igor P Pogribny
Hepatocellular carcinoma (HCC) is the fastest-rising cause of cancer-related death in the United States. Recent epidemiological studies have identified nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease (NAFLD), as a major risk factor for HCC. Elucidating the underlying mechanisms associated with the development of NASH-derived HCC is critical for identifying early biomarkers for the progression of the disease and for treatment and prevention. In the present study, using liver samples from C57BL/6J mice submitted to the Stelic Animal Model (STAM) of NASH-associated liver carcinogenesis, we investigated the role of microRNA (miRNA) alterations in the pathogenesis of NASH-derived HCC...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29177004/active-fraction-hs7-from-taiwanofungus-camphoratus-inhibits-akt-mtor-erk-and-stat3-pathways-and-induces-cdk-inhibitors-in-cl1-0-human-lung-cancer-cells
#13
I-Chun Lai, Gi-Ming Lai, Jyh-Ming Chow, Hsin-Lun Lee, Chuan-Feng Yeh, Chi-Han Li, Jiann-Long Yan, Shuang-En Chuang, Jacqueline Whang-Peng, Kuan-Jen Bai, Chih-Jung Yao
Background: The non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. In NSCLC, the oncogenic AKT-mTOR, ERK and STAT3 pathways are commonly dysregulated and have emerged as attractive targets for therapeutic developments. In a relatively limited subset of NSCLC, these pathways driven by mutant EGFR can be treated by the tyrosine kinase inhibitors (TKIs)-mediated targeted therapy. However, for the most NSCLC, more novel targeted agents are imperatively needed...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/29175420/%C3%AE-1a-adrenoceptors-activate-mtor-signalling-and-glucose-uptake-in-cardiomyocytes
#14
Masaaki Sato, Bronwyn A Evans, Anna L Sandström, Ling Yeong Chia, Saori Mukaida, Bui San Thai, Anh Nguyen, Linzi Lim, Christina Yr Tan, Jo-Anne Baltos, Paul J White, Lauren T May, Dana S Hutchinson, Roger J Summers, Tore Bengtsson
The capacity of G protein-coupled receptors to modulate mammalian target of rapamycin (mTOR) activity is a newly emerging paradigm with the potential to link cell surface receptors with cell survival. Cardiomyocyte viability is linked to signaling pathways involving Akt and mTOR, as well as increased glucose uptake and utilization. Our aim was to determine whether the α1A-adrenoceptor (AR) couples to these protective pathways, and increased glucose uptake. We characterised α1A-AR signalling in CHO-K1 cells co-expressing the human α1A-AR and GLUT4 (CHOα1AGLUT4myc) and in neonatal rat ventricular cardiomyocytes (NRVM), and measured glucose uptake, intracellular Ca2+ mobilization, and phosphorylation of mTOR, Akt, 5' adenosine monophosphate-activated kinase (AMPK) and S6 ribosomal protein...
November 23, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29171041/traf6-regulates-proliferation-of-stromal-cells-in-the-transition-and-peripheral-zones-of-benign-prostatic-hyperplasia-via-akt-mtor-signaling
#15
Yun-Feng Shi, Dian-Jun Yu, Chen-Yi Jiang, Xing-Jie Wang, Yi-Ping Zhu, Rui-Zhe Zhao, Zhong Lv, Xiao-Wen Sun
BACKGROUND: Increased prostatic smooth muscle tone and hyperplastic growth contribute to urethral obstruction and voiding symptoms in benign prostatic hyperplasia (BPH). It has been suggested that different proliferative potential of stromal cells between transition zone (TZ) and adjoining regions of the prostate plays a significant role in the development of BPH. However, the molecular mechanisms of this hyperplastic process remain unclear. We found tumor necrosis factor receptor-associated factor 6 (TRAF6) highly expressed in TZ stromal cells compared to peripheral zone (PZ) stromal cells by gene array analyzes...
November 23, 2017: Prostate
https://www.readbyqxmd.com/read/29167824/protein-activation-mapping-of-human-sun-protected-epidermis-after-an-acute-dose-of-erythemic-solar-simulated-light
#16
Janine G Einspahr, Clara Curiel-Lewandrowski, Valerie S Calvert, Steven P Stratton, David S Alberts, James Warneke, Chengcheng Hu, Kathylynn Saboda, Elisabeth L Wagener, Sally Dickinson, Zigang Dong, Ann M Bode, Emanuel F PetricoinIII
Ultraviolet radiation is an important etiologic factor in skin cancer and a better understanding of how solar stimulated light (SSL) affects signal transduction pathways in human skin which is needed in further understanding activated networks that could be targeted for skin cancer prevention. We utilized Reverse Phase Protein Microarray Analysis (RPPA), a powerful technology that allows for broad-scale and quantitative measurement of the activation/phosphorylation state of hundreds of key signaling proteins and protein pathways in sun-protected skin after an acute dose of two minimal erythema dose (MED) of SSL...
2017: NPJ Precision Oncology
https://www.readbyqxmd.com/read/29164996/cptp-a-sphingolipid-transfer-protein-that-regulates-autophagy-and-inflammasome-activation
#17
Shrawan Kumar Mishra, Yong-Guang Gao, Yibin Deng, Charles E Chalfant, Edward H Hinchcliffe, Rhoderick E Brown
The macroautophagy/autophagy and inflammasome pathways are linked through their roles in innate immunity and chronic inflammatory disease. Ceramide-1-phosphate (C1P) is a bioactive sphingolipid that regulates pro-inflammatory eicosanoid production. Whether C1P also regulates autophagy and inflammasome assembly/activation is not known. Here we show that CPTP (a protein that traffics C1P from its site of phosphorylation in the trans-Golgi to target membranes) regulates both autophagy and inflammasome activation...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29163766/epigallocatechin-3-gallate-egcg-up-regulates-mir-15b-expression-thus-attenuating-store-operated-calcium-entry-soce-into-murine-cd4-t-cells-and-human-leukaemic-t-cell-lymphoblasts
#18
Shaqiu Zhang, Tamer Al-Maghout, Rosi Bissinger, Ni Zeng, Lisann Pelzl, Madhuri S Salker, Anchun Cheng, Yogesh Singh, Florian Lang
CD4(+) T cells are key elements in immune responses and inflammation. Activation of T cell receptors in CD4(+) T cells triggers cytosolic Ca(2+) release with subsequent store operated Ca(2+) entry (SOCE), which is accomplished by the pore forming Ca(2+) release activated Ca(2+) (CRAC) channel Orai1 and its regulator stromal cell-interaction molecule 2 (STIM2). Green tea polyphenol epigallocatechin-3-gallate (EGCG) acts as a potent anti-inflammatory and anti-oxidant agent for various types of cells including immune cells...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163135/neuroprotective-effect-of-ligustilide-through-induction-of-%C3%AE-secretase-processing-of-both-app-and-klotho-in-a-mouse-model-of-alzheimer-s-disease
#19
Xi Kuang, Hong-Jing Zhou, Amy H Thorne, Xi-Nan Chen, Lin-Jiao Li, Jun-Rong Du
Emerging evidence suggests that alpha-processing single transmembrane proteins, amyloid precursor protein (APP) and anti-aging protein Klotho, are likely to be involved in the progression of Alzheimer's disease (AD). The natural phthalide Ligustilide (LIG) has been demonstrated to protect against aging- and amyloid-β (Aβ)-induced brain dysfunction in animal models. The present study is to investigate the effects of LIG on cognitive deficits and metabolism of both APP and Klotho and its underlying mechanism in AD double-transgenic (APP/PS1) mice and cultured human cells...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29162840/whey-protein-concentrate-renders-mda-mb-231-cells-sensitive-to-rapamycin-by-altering-cellular-redox-state-and-activating-gsk3%C3%AE-mtor-signaling
#20
Shih-Hsuan Cheng, Yang-Ming Tseng, Szu-Hsien Wu, Shih-Meng Tsai, Li-Yu Tsai
Whey protein concentrate (WPC) is an amino acid-rich supplement that has been shown to increase cellular antioxidant capacity. Mammalian target of rapamycin (mTOR) is a crucial regulator of signaling in mammalian cells, and serves as a therapeutic target for triple-negative breast cancer (TNBC). This study was designed to investigate the effect of combining WPC with rapamycin on MDA-MB-231 human breast cancer cells. These cells were found to be insensitive to rapamycin and exhibited higher glutathione (GSH) and reactive oxygen species levels than non-tumorigenic MCF-10A cells...
November 21, 2017: Scientific Reports
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