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mtor protein, human

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https://www.readbyqxmd.com/read/28640831/ribosomal-dna-copy-number-loss-and-sequence-variation-in-cancer
#1
Baoshan Xu, Hua Li, John M Perry, Vijay Pratap Singh, Jay Unruh, Zulin Yu, Musinu Zakari, William McDowell, Linheng Li, Jennifer L Gerton
Ribosomal DNA is one of the most variable regions in the human genome with respect to copy number. Despite the importance of rDNA for cellular function, we know virtually nothing about what governs its copy number, stability, and sequence in the mammalian genome due to challenges associated with mapping and analysis. We applied computational and droplet digital PCR approaches to measure rDNA copy number in normal and cancer states in human and mouse genomes. We find that copy number and sequence can change in cancer genomes...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28634370/microbial-antigens-stimulate-metalloprotease-7-secretion-in-human-b-lymphocytes-using-mtor-dependent-and-independent-pathways
#2
Mohamed F Ali, Harika Dasari, Virginia P Van Keulen, Divi Cornec, George Vasmatzis, Tobias Peikert, Eva M Carmona
Metalloproteinases (MMPs) contribute to tissue remodeling and acute inflammation not only by degrading extracellular matrix proteins but also by controlling the influx of chemokines through the regulation and shedding of syndecans. B-lymphocytes, in addition to their well-known function as antibody producing cells, participate in the innate immune response by secreting inflammatory cytokines and chemokines. However, there is little information about the role of B-lymphocytes in the regulation of MMPs; consequently, herein we investigated whether activated human circulating B-lymphocytes contributed to the secretion of MMPs...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633336/a278c-mutation-of-dihydropteridine-reductase-decreases-autophagy-via-mtor-signaling
#3
Qin Si, Sifan Sun, Yanting Gu
Dihydropteridine reductase (QDPR) plays an important role in the recycling of BH4 and is closely related to oxidative stress. We have previously reported that the overexpression of QDPR in human kidney HEK293T cells significantly protected against oxidative stress, and these beneficial effects were abolished by A278C mutation. To evaluate the effect of wild-type and mutant QDPR on autophagy and its mechanism in HEK293T cells, we constructed the wild-type and mutant QDPR expression plasmids and transfected them into HEK293T cells...
June 15, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28632723/mir-646-inhibited-cell-proliferation-and-emt-induced-metastasis-by-targeting-foxk1-in-gastric-cancer
#4
P Zhang, W M Tang, H Zhang, Y Q Li, Y Peng, J Wang, G N Liu, X T Huang, J J Zhao, G Li, A M Li, Y Bai, Y Chen, Y X Ren, G X Li, Y D Wang, S D Liu, J D Wang
BACKGROUND: MiR-646 has been reported to be aberrantly expressed in human cancers. However, the underlying molecular mechanisms of action of miR-646 in gastric cancer (GC) have not yet been investigated. METHODS: In vitro function of miR-646 in GC was evaluated using EdU assay, plate colony formation assay, and matrigel invasion assay. Real-time PCR or western blotting was performed to detect miR-646 and FOXK1 expressions. In vivo tumour growth and metastasis were conducted in nude mice...
June 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28632179/the-antiproliferative-effect-of-cyclodipeptides-from-pseudomonas-aeruginosa-pao1-on-hela-cells-involves-inhibition-of-phosphorylation-of-akt-and-s6k-kinases
#5
Laura Hernández-Padilla, Dolores Vázquez-Rivera, Luis A Sánchez-Briones, Alma L Díaz-Pérez, José Moreno-Rodríguez, Mario A Moreno-Eutimio, Victor Meza-Carmen, Homero Reyes-De la Cruz, Jesús Campos-García
Pseudomonas aeruginosa PAO1, a potential pathogen of plants and animals, produces the cyclodipeptides cyclo(l-Pro-l-Tyr), cyclo(l-Pro-l-Phe), and cyclo(l-Pro-l-Val) (PAO1-CDPs), whose effects have been implicated in inhibition of human tumor cell line proliferation. Our purpose was to investigate in depth in the mechanisms of HeLa cell proliferation inhibition by the PAO1-CDPs. The results indicate that PAO1-CDPs, both purified individually and in mixtures, inhibited HeLa cell proliferation by arresting the cell cycle at the G0-G1 transition...
June 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28631572/endoplasmic-reticulum-stress-could-induce-autophagy-and-apoptosis-and-enhance-chemotherapy-sensitivity-in-human-esophageal-cancer-ec9706-cells-by-mediating-pi3k-akt-mtor-signaling-pathway
#6
Fang Zhou, Yan-Hua Li, Jian-Jun Wang, Jia Pan, Hong Lu
The study was designed to explore the mechanism of tunicamycin-induced endoplasmic reticulum stress in human esophageal cancer EC9706 cells and EC109 cells, as well as its effects on cell autophagy, apoptosis, and chemoresistance. Tunicamycin-induced endoplasmic reticulum stress model was established in EC9706 and EC109 cell lines. Western blotting was employed to detect the expression of endoplasmic reticulum stress iconic protein GRP78. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate the effect of different cisplatin and tunicamycin concentrations on survival rate of EC9706 cells and EC109 cells...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28628306/lysine-deacetylation-by-hdac6-regulates-the-kinase-activity-of-akt-in-human-neural-progenitor-cells
#7
Jonathan Iaconelli, Jasmin Lalonde, Bradley Watmuff, Bangyan Liu, Ralph Mazitschek, Stephen J Haggarty, Rakesh Karmacharya
AKT family of serine-threonine kinases functions downstream of phosphatidylinositol 3-kinase (PI3K) to transmit signals by direct phosphorylation of a number of targets, including the mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β) and β-catenin. AKT binds to phosphatidylinositol (3,4,5)-triphosphate (PIP3) generated by PI3K activation, which results in its membrane localization and subsequent activation through phosphorylation by phosphoinositide-dependent protein kinase 1 (PDK1)...
June 19, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28627676/luteolin-inhibits-angiogenesis-by-blocking-gas6-axl-signaling-pathway
#8
Xiaobo Li, Minfeng Chen, Xueping Lei, Maohua Huang, Wencai Ye, Rijia Zhang, Dongmei Zhang
Growth arrest-specific protein 6 (Gas6) induces the activation of Axl receptor tyrosine kinase (Axl), which plays an important role in angiogenic processes, including proliferation, migration, invasion, tube formation and pericyte recruitment of endothelial cells. The inhibition of Gas6/Axl pathway has been demonstrated to be an effective anti-angiogenic therapy. Luteolin, which is a natural active flavonoid, has been reported to possess anti-angiogenic effects. However, the underlying mechanism of luteolin in anti-angiogenesis is not fully understood...
June 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28625796/the-characterization-of-rheb-gene-and-its-responses-to-hypoxia-and-thermal-stresses-in-the-small-abalone-haliotis-diversicolor
#9
Lianghua He, Xin Zhang, Ying Huang, Huiping Yang, Yilei Wang, Ziping Zhang
RHEB (Ras Homolog Enriched in Brain) is a GTP-binding protein that is ubiquitously expressed in humans and other mammals. The protein is largely involved in the mechanistic target of rapamycin (mTOR) pathway, and regulates the cell cycle progression and growth. The goal of this study was to characterize the RHEB gene in the small abalone Haliotis diversicolor, and identify the responses of RHEB gene to stresses of hypoxia or/and thermal. The objectives were to: 1) clone the full-length cDNA RHEB gene in the H...
June 15, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28618450/sav1-represses-the-development-of-human-colorectal-cancer-by-regulating-the-akt-mtor-pathway-in-a-yap-dependent-manner
#10
Jianwu Jiang, Wei Chang, Yang Fu, Yongshun Gao, Chunlin Zhao, Xiefu Zhang, Shuijun Zhang
OBJECTIVES: SAV1 is a human homologue of Salvador that contains two protein-protein interaction modules known as WW domains and acts as a scaffolding protein. SAV1 participates in the development of diverse types of cancer. We aimed to investigate the role of SAV1 in human colorectal cancer. MATERIALS AND METHODS: Human colorectal cancer samples were used to study the expression of SAV1 and YAP. Loss-of-function and gain-of-function strategies were used to study the effects of SAV1 on colorectal cancer cell growth...
June 15, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28617309/lipid-storage-and-autophagy-in-melanoma-cancer-cells
#11
Claudia Giampietri, Simonetta Petrungaro, Martina Cordella, Claudio Tabolacci, Luana Tomaipitinca, Antonio Facchiano, Adriana Eramo, Antonio Filippini, Francesco Facchiano, Elio Ziparo
Cancer stem cells (CSC) represent a key cellular subpopulation controlling biological features such as cancer progression in all cancer types. By using melanospheres established from human melanoma patients, we compared less differentiated melanosphere-derived CSC to differentiating melanosphere-derived cells. Increased lipid uptake was found in melanosphere-derived CSC vs. differentiating melanosphere-derived cells, paralleled by strong expression of lipogenic factors Sterol Regulatory Element-Binding Protein-1 (SREBP-1) and Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ)...
June 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28615679/combination-of-rad001-everolimus-and-docetaxel-reduces-prostate-and-breast-cancer-cell-vegf-production-and-tumour-vascularisation-independently-of-sphingosine-kinase-1
#12
Heba Alshaker, Qi Wang, Torsten Böhler, Robert Mills, Mathias Winkler, Tawfiq Arafat, Yoshiaki Kawano, Dmitri Pchejetski
Resistance to docetaxel is a key problem in current prostate and breast cancer management. We have recently discovered a new molecular mechanism of prostate cancer docetaxel chemoresistance mediated by the mammalian target of rapamycin (mTOR)/sphingosine-kinase-1 (SK1) pathway. Here we investigated the influence of this pathway on vascular endothelial growth factor (VEGF) production and tumour vascularisation in hormone resistant prostate and breast cancer models. Immunofluorescent staining of tumour sections from human oestrogen receptor (ER)-negative breast cancer patients showed a strong correlation between phosphorylated P70S6 kinase (mTOR downstream target), VEGF and SK1 protein expression...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615245/the-regulatory-1%C3%AE-subunit-of-protein-kinase-a-modulates-renal-cystogenesis
#13
Hong Ye, Xiaofang Wang, Megan M Constans, Caroline R Sussman, Fouad Chebib, Maria V Irazabal, William F Young, Peter C Harris, Lawrence S Kirschner, Vicente E Torres
The failure of the polycystins (PCs) to function in primary cilia is thought to be responsible for Autosomal Dominant Polycystic Kidney Disease (ADPKD). Primary cilia integrate multiple cellular signaling pathways, including calcium, cAMP, Wnt, and Hedgehog, which control cell proliferation and differentiation. It has been proposed that mutated PCs result in reduced intracellular calcium, which in turn upregulates cAMP, protein kinase A (PKA) signaling, and subsequently other proliferative signaling pathways...
June 14, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28613975/activation-of-drd5-dopamine-receptor-d5-inhibits-tumor-growth-by-autophagic-cell-death
#14
Zhi Gen Leng, Shao Jian Lin, Ze Rui Wu, Yu Hang Guo, Lin Cai, Han Bing Shang, Hao Tang, Ya Jun Xue, Mei Qing Lou, Wenxiu Zhao, Wei-Dong Le, Wei Guo Zhao, Xun Zhang, Zhe Bao Wu
Dopamine agonists such as bromocriptine and cabergoline have been successfully used in the treatment of pituitary prolactinomas and other neuroendocrine tumors. However, their therapeutic mechanisms are not fully understood. In this study we demonstrated that DRD5 (dopamine receptor D5) agonists were potent inhibitors of pituitary tumor growth. We further found that DRD5 activation increased production of reactive oxygen species (ROS), inhibited the MTOR pathway, induced macroautophagy/autophagy, and led to autophagic cell death (ACD) in vitro and in vivo...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28610844/overexpression-of-eif4f-components-in-meningiomas-and-suppression-of-meningioma-cell-growth-by-inhibiting-translation-initiation
#15
REVIEW
Janet L Oblinger, Sarah S Burns, Jie Huang, Li Pan, Yulin Ren, Rulong Shen, A Douglas Kinghorn, D Bradley Welling, Long-Sheng Chang
Meningiomas frequently display activation of the PI3K/AKT/mTOR pathway, leading to elevated levels of phospho-4E binding proteins, which enhances protein synthesis; however, it is not known whether inhibition of protein translation is an effective treatment option for meningiomas. We found that human meningiomas expressed high levels of the three components of the eukaryotic initiation factor 4F (eIF4F) translation initiation complex, eIF4A, eIF4E, and eIF4G. The expression of eIF4A and eIF4E was important in sustaining the growth of NF2-deficient benign meningioma Ben-Men-1 cells, as shRNA-mediated knockdown of these proteins strongly reduced cell proliferation...
June 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28607460/recombinant-thrombomodulin-exerts-anti-autophagic-action-in-endothelial-cells-and-provides-anti-atherosclerosis-effect-in-apolipoprotein-e-deficient-mice
#16
Po-Sheng Chen, Kuan-Chieh Wang, Ting-Hsing Chao, Hsing-Chun Chung, Shi-Ya Tseng, Chawn-Yau Luo, Guey-Yueh Shi, Hua-Lin Wu, Yi-Heng Li
Stress-induced alteration in endothelial cells (ECs) integrity precedes the development of atherosclerosis. Previous studies showed that the soluble recombinant thrombomodulin (rTM) not only increases ECs proliferation but also exerts anti-apoptotic activity in ECs. However, the functional significance of soluble rTM on autophagy-related apoptosis in ECs is still undetermined. Implicating a cytoprotective role for rTM in persistent serum starvation (SS)-induced autophagy in cultured ECs, we found that treatment of rTM decreased the expression of SS-induced autophagy-related proteins, ATG5 and LC3, and the formation of autophagosomes through activation of AKT/mTOR pathway...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606928/mtor-controls-chrebp-transcriptional-activity-and-pancreatic-%C3%AE-cell-survival-under-diabetic-stress
#17
Gia Cac Chau, Dong Uk Im, Tong Mook Kang, Jeong Mo Bae, Won Kim, Suhkneung Pyo, Eun-Yi Moon, Sung Hee Um
Impaired nutrient sensing and dysregulated glucose homeostasis are common in diabetes. However, how nutrient-sensitive signaling components control glucose homeostasis and β cell survival under diabetic stress is not well understood. Here, we show that mice lacking the core nutrient-sensitive signaling component mammalian target of rapamycin (mTOR) in β cells exhibit reduced β cell mass and smaller islets. mTOR deficiency leads to a severe reduction in β cell survival and increased mitochondrial oxidative stress in chemical-induced diabetes...
June 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28600528/overexpression-of-rasd1-inhibits-glioma-cell-migration-invasion-and-inactivates-the-akt-mtor-signaling-pathway
#18
Shangfeng Gao, Lei Jin, Guangping Liu, Peng Wang, Zonghan Sun, Yujia Cao, Hengliang Shi, Xuejiao Liu, Qiong Shi, Xiuping Zhou, Rutong Yu
The RAS signaling pathway is hyperactive in malignant glioma due to overexpression and/or increased activity. A previous study identified that RASD1, a member of the RAS superfamily of small G-proteins, is a significantly dysregulated gene in oligodendroglial tumors that responded to chemotherapy. However, the role and mechanism of RASD1 in the progression of human glioma remain largely unknown. In the present study, by analyzing a public genomics database, we found that high levels of RASD1 predicted good survival of astrocytoma patients...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28600122/oxidative-stress-plays-a-key-role-in-butyrate-mediated-autophagy-via-akt-mtor-pathway-in-hepatoma-cells
#19
Kishor Pant, Anoop Saraya, Senthil K Venugopal
Hepatocellular Carcinoma (HCC) is one of the most aggressive forms of cancer, responsible for a number of deaths in humans. Butyrate, one of the short chain fatty acids produced by the gut microbiota during anaerobic fermentation, was shown to be beneficial for inhibiting cancer growth. In this study, we showed that sodium butyrate induced autophagy via reactive oxygen species (ROS) in hepatoma cells. Butyrate (0-6 mM) incubation significantly increased intracellular ROS levels (45.2% compared to control), which in turn inhibited phosphorylation of akt and mTOR, leading to the upregulation of autophagic proteins, such as beclin 1, ATG 5, LC3-II, followed by the increased autophagosome formation (34...
June 11, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28599494/cucurbitacin-e-induces-apoptosis-of-human-prostate-cancer-cells-via-cofilin-1-and-mtorc1
#20
Xiaolong He, Qi Gao, Yayong Qiang, Wei Guo, Yadong Ma
Cucurbitacin E is an important member of the cucurbitacin family and exhibits inhibitory effects in various types of cancer. Cucurbitacin is a potential antineoplastic drug; however, its anticancer effect in human prostate cancer (PC) remains unknown. The aim of the present study was to determine whether the effect of cucurbitacin E on the cell viability and apoptosis of the human PC cell line, LNCaP, was mediated by cofilin-1- and mammalian target of rapamycin (mTOR). The results of the present study demonstrated that cucurbitacin E significantly exhibited cytotoxicity, suppressed cell viability (P<0...
June 2017: Oncology Letters
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