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Metabolic reprogramming

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https://www.readbyqxmd.com/read/28087256/manganese-superoxide-dismutase-and-glutathione-peroxidase-1-contribute-to-the-rise-and-fall-of-mitochondrial-reactive-oxygen-species-which-drive-oncogenesis
#1
REVIEW
Dede N Ekoue, Chenxia He, Alan M Diamond, Marcelo G Bonini
Reactive oxygen species (ROS) largely originating in the mitochondria play essential roles in the metabolic and (epi)genetic reprogramming of cancer cell evolution towards more aggressive phenotypes. Recent studies have indicated that the activity of superoxide dismutase (SOD2) may promote tumor progression by serving as a source of hydrogen peroxide (H2O2). H2O2 is a form of ROS that is particularly active as a redox agent affecting cell signaling due to its ability to freely diffuse out of the mitochondria and alter redox active amino acid residues on regulatory proteins...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28076886/the-ectomycorrhizal-basidiomycete-hebeloma-cylindrosporum-undergoes-early-waves-of-transcriptional-reprogramming-prior-to-symbiotic-structures-differentiation
#2
Jeanne Doré, Annegret Kohler, Audrey Dubost, Hope Hundley, Vasanth Singan, Yi Peng, Alan Kuo, Igor V Grigoriev, Francis Martin, Roland Marmeisse, And Gilles Gay
To clarify the early molecular interaction between ectomycorrhizal partners, we performed a RNA-Seq study of transcriptome reprogramming of the basidiomycete Hebeloma cylindrosporum before symbiotic structure differentiation with Pinus pinaster. Mycorrhiza transcriptome was studied for comparison. By reference to asymbiotic mycelium, 47 and 46 genes were specifically up-regulated over five-fold (p≤0.05) upon rhizosphere colonization and root adhesion respectively. Other 45 were up-regulated throughout the symbiotic interaction, from rhizosphere colonization to differentiated mycorrhizas, whereas 274 were specifically up-regulated in mycorrhizas...
January 11, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28073003/employing-metabolism-to-improve-the-diagnosis-and-treatment-of-pancreatic-cancer
#3
REVIEW
Christopher J Halbrook, Costas A Lyssiotis
Pancreatic ductal adenocarcinoma is on pace to become the second leading cause of cancer-related death. The high mortality rate results from a lack of methods for early detection and the inability to successfully treat patients once diagnosed. Pancreatic cancer cells have extensively reprogrammed metabolism, which is driven by oncogene-mediated cell-autonomous pathways, the unique physiology of the tumor microenvironment, and interactions with non-cancer cells. In this review, we discuss how recent efforts delineating rewired metabolic networks in pancreatic cancer have revealed new in-roads to develop detection and treatment strategies for this dreadful disease...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28071704/high-fat-diet-induced-changes-of-mouse-hepatic-transcription-and-enhancer-activity-can-be-reversed-by-subsequent-weight-loss
#4
Majken Siersbæk, Lyuba Varticovski, Shutong Yang, Songjoon Baek, Ronni Nielsen, Susanne Mandrup, Gordon L Hager, Jay H Chung, Lars Grøntved
Epigenetic factors have been suggested to play an important role in metabolic memory by trapping and maintaining initial metabolic changes within the transcriptional regulatory machinery. In this study we fed mice a high fat diet (HFD) for seven weeks followed by additional five weeks of chow, to identify HFD-mediated changes to the hepatic transcriptional program that may persist after weight loss. Mice fed a HFD displayed increased fasting insulin levels, hepatosteatosis and major changes in hepatic gene transcription associated with modulation of H3K27Ac at enhancers, but no significant changes in chromatin accessibility, indicating that HFD-regulated gene transcription is primarily controlled by modulating the activity of pre-established enhancers...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069379/ndrg2-overexpression-suppresses-hepatoma-cells-survival-during-metabolic-stress-through-disturbing-the-activation-of-fatty-acid-oxidation
#5
Tao Pan, Mei Zhang, Fang Zhang, Guang Yan, Yi Ru, Qinhao Wang, Yao Zhang, Xuehui Wei, Xinyuan Xu, Lan Shen, Jian Zhang, Kaichun Wu, Libo Yao, Xia Li
Because of the high nutrient consumption and inadequate vascularization, solid tumor constantly undergoes metabolic stress during tumor development. Oncogenes and tumor suppressor genes participated in cancer cells' metabolic reprogramming. N-Myc downstream regulated gene 2 (NDRG2) is a recently identified tumor suppressor gene, but its function in cancer metabolism, particularly during metabolic stress, remains unclear. In this study, we found that NDRG2 overexpression significantly reduced hepatoma cell proliferation and enhanced cell apoptosis under glucose limitation...
January 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28068482/metabolic-reprogramming-in-brain-tumors
#6
Sriram Venneti, Craig B Thompson
Next-generation sequencing has substantially enhanced our understanding of the genetics of primary brain tumors by uncovering several novel driver genetic alterations. How many of these genetic modifications contribute to the pathogenesis of brain tumors is not well understood. An exciting paradigm emerging in cancer biology is that oncogenes actively reprogram cellular metabolism to enable tumors to survive and proliferate. We discuss how some of these genetic alterations in brain tumors rewire metabolism...
December 21, 2016: Annual Review of Pathology
https://www.readbyqxmd.com/read/28065746/linking-metabolic-reprogramming-to-therapy-resistance-in-cancer
#7
REVIEW
Andrea Morandi, Stefano Indraccolo
Metabolic rearrangements are essential to satisfy the different requirements of cancer cells during tumorigenesis and recent studies have highlighted a role for such metabolic reprogramming in response and adaptation to therapies. However, therapy-resistant experimental models have been described to be either glycolysis-dependent or OXPHOS-addicted. Here we discuss the recent literature on metabolic reprogramming of cancer in therapy resistance with a plausible explanation of the observed differences which collectively indicate that dis-regulated metabolic pathways could be considered a potential therapeutic target in tumors resistant to conventional therapy...
January 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28055029/gastrointestinal-transcriptomic-response-of-metabolic-vitamin-b12-pathways-in-roux-en-y-gastric-bypass
#8
Priscila Sala, Giliane Belarmino, Raquel S Torrinhas, Natasha M Machado, Danielle C Fonseca, Graziela R Ravacci, Robson K Ishida, Ismael F M S Guarda, Eduardo G de Moura, Paulo Sakai, Marco A Santo, Ismael D C G da Silva, Claudia C A Pereira, Angela F Logullo, Steven Heymsfield, Daniel Giannella-Neto, Dan L Waitzberg
OBJECTIVES: Vitamin B12 (B12) deficiency after Roux-en-Y gastric bypass (RYGB) is highly prevalent and may contribute to postoperative complications. Decreased production of intrinsic factor owing to gastric fundus removal is thought to have a major role, but other components of B12 metabolism may also be affected. We evaluated changes in the expression levels of multiple B12 pathway-encoding genes in gastrointestinal (GI) tissues to evaluate the potential roles in contributing to post-RYGB B12 deficiency...
January 5, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28054552/c-src-phosphorylation-and-activation-of-hexokinase-promotes-tumorigenesis-and-metastasis
#9
Jia Zhang, Suili Wang, Bin Jiang, Lihong Huang, Zhiliang Ji, Xiaotong Li, Huamin Zhou, Aidong Han, Ai Chen, Yanan Wu, Huanhuan Ma, Wentao Zhao, Qingwen Zhao, Changchuan Xie, Xiaoyan Sun, Yanming Zhou, Huiying Huang, Muhammad Suleman, Furong Lin, Lin Zhou, Fang Tian, Meijun Jin, Yana Cai, Nan Zhang, Qinxi Li
It is well known that c-Src has important roles in tumorigenesis. However, it remains unclear whether c-Src contributes to metabolic reprogramming. Here we find that c-Src can interact with and phosphorylate hexokinases HK1 and HK2, the rate-limiting enzymes in glycolysis. Tyrosine phosphorylation dramatically increases their catalytic activity and thus enhances glycolysis. Mechanistically, c-Src phosphorylation of HK1 at Tyr732 robustly decreases its Km and increases its Vmax by disrupting its dimer formation...
January 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28053954/targeting-lipid-metabolic-reprogramming-as-anticancer-therapeutics
#10
REVIEW
Ji-Young Cha, Ho-Jae Lee
Cancer cells rewire their metabolism to satisfy the demands of growth and survival, and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. Lipid metabolism is pivotal in cellular process that converts nutrients into energy, building blocks for membrane biogenesis and the generation of signaling molecules. Accumulating evidence suggests that cancer cells show alterations in different aspects of lipid metabolism. The changes in lipid metabolism of cancer cells can affect numerous cellular processes, including cell growth, proliferation, differentiation, and survival...
December 2016: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28049629/integrated-metabolomics-and-proteomics-highlight-altered-nicotinamide-and-polyamine-pathways-in-lung-adenocarcinoma
#11
REVIEW
Johannes F Fahrmann, Dmitry D Grapov, Kwanjeera Wanichthanarak, Brian C DeFelice, Michelle R Salemi, William N Rom, David R Gandara, Brett S Phinney, Oliver Fiehn, Harvey Pass, Suzanne Miyamoto
Lung cancer is the leading cause of cancer mortality in the United States with non-small cell lung cancer (NSCLC) adenocarcinoma being the most common histological type. Early perturbations in cellular metabolism are a hallmark of cancer, but the extent of these changes in early stage lung adenocarcinoma remains largely unknown. In the current study, an integrated metabolomics and proteomics approach was utilized to characterize the biochemical and molecular alterations between malignant and matched control tissue from 27 subjects diagnosed with early stage lung adenocarcinoma...
January 3, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28042046/rational-design-of-selective-allosteric-inhibitors-of-phgdh-and-serine-synthesis-with-anti-tumor-activity
#12
Qian Wang, Maria V Liberti, Pei Liu, Xiaobing Deng, Ying Liu, Jason W Locasale, Luhua Lai
Metabolic reprogramming in cancer cells facilitates growth and proliferation. Increased activity of the serine biosynthetic pathway through the enzyme phosphoglycerate dehydrogenase (PHGDH) contributes to tumorigenesis. With a small substrate and a weak binding cofactor, (NAD(+)), inhibitor development for PHGDH remains challenging. Instead of targeting the PHGDH active site, we computationally identified two potential allosteric sites and virtually screened compounds that can bind to these sites. With subsequent characterization, we successfully identified PHGDH non-NAD(+)-competing allosteric inhibitors that attenuate its enzyme activity, selectively inhibit de novo serine synthesis in cancer cells, and reduce tumor growth in vivo...
December 20, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/28041958/srebp1-contributes-to-resolution-of-pro-inflammatory-tlr4-signaling-by-reprogramming-fatty-acid-metabolism
#13
Yumiko Oishi, Nathanael J Spann, Verena M Link, Evan D Muse, Tobias Strid, Chantle Edillor, Matthew J Kolar, Takashi Matsuzaka, Sumio Hayakawa, Jenhan Tao, Minna U Kaikkonen, Aaron F Carlin, Michael T Lam, Ichiro Manabe, Hitoshi Shimano, Alan Saghatelian, Christopher K Glass
Macrophages play pivotal roles in both the induction and resolution phases of inflammatory processes. Macrophages have been shown to synthesize anti-inflammatory fatty acids in an LXR-dependent manner, but whether the production of these species contributes to the resolution phase of inflammatory responses has not been established. Here, we identify a biphasic program of gene expression that drives production of anti-inflammatory fatty acids 12-24 hr following TLR4 activation and contributes to downregulation of mRNAs encoding pro-inflammatory mediators...
December 21, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28040803/oncogenic-regulation-of-tumor-metabolic-reprogramming
#14
Míriam Tarrado-Castellarnau, Pedro de Atauri, Marta Cascante
Development of malignancy is accompanied by a complete metabolic reprogramming closely related to the acquisition of most of cancer hallmarks. In fact, key oncogenic pathways converge to adapt the metabolism of carbohydrates, proteins, lipids and nucleic acids to the dynamic tumor microenvironment, conferring a selective advantage to cancer cells. Therefore, metabolic properties of tumor cells are significantly different from those of non-transformed cells. In addition, tumor metabolic reprogramming is linked to drug resistance in cancer treatment...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/28040634/insights-on-germinability-and-desiccation-tolerance-in-developing-neem-seeds-azadirachta-indica-role-of-aos-antioxidative-enzymes-and-dehydrin-like-protein
#15
Balram Sahu, Alok Kumar Sahu, Srinivasa Rao Chennareddy, Avinash Soni, Subhash Chandra Naithani
The germinability and desiccation tolerance (DT) in developing seed are regulated by cellular metabolism involving active oxygen species (AOS) and protective proteins during maturation drying. The aim of the present investigation was to unravel the functions of AOS (superoxide, H2O2 and OH-radical), antioxidative enzymes (SOD, CAT and APX) and dehydrin-like proteins in regulating the germinability and DT in undried and artificially desiccated developing neem seeds. Germination was first observed in seeds of 8 weeks after anthesis (waa) whereas DT was noticed from 9 waa...
December 25, 2016: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28039486/cd147-a-small-molecule-transporter-ancillary-protein-at-the-crossroad-of-multiple-hallmarks-of-cancer-and-metabolic-reprogramming
#16
Agnieszka A Kendrick, Johnathon Schafer, Monika Dzieciatkowska, Travis Nemkov, Angelo D Alessandro, Deepika Neelakantan, Heide L Ford, Chad G Pearson, Colin D Weekes, Kirk C Hansen, Elan Z Eisenmesser
Increased expression of CD147 in pancreatic cancer has been proposed to play a critical role in cancer progression via CD147 chaperone function for lactate monocarboxylate transporters (MCTs). Here, we show for the first time that CD147 interacts with membrane transporters beyond MCTs and exhibits a protective role for several of its interacting partners. CD147 prevents its interacting partner's proteasome-dependent degradation and correct plasma membrane localization through CD147 transmembrane (TM) region...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039459/a-novel-glutaminase-inhibitor-968-inhibits-the-migration-and-proliferation-of-non-small-cell-lung-cancer-cells-by-targeting-egfr-erk-signaling-pathway
#17
Tianyu Han, Meng Guo, Tingting Zhang, Mingxi Gan, Caifeng Xie, Jian-Bin Wang
Metabolic reprogramming is critical for cancer cell proliferation. Glutaminolysis which provides cancer cells with bioenergetics and intermediates for macromolecular synthesis have been intensively studied in recent years. Glutaminase C (GAC) is the first and rate-limiting enzyme in glutaminolysis and plays important roles in cancer initiation and progression. We previously screened a small molecule named 968, a specific inhibitor of GAC, to block the proliferation of human breast cancer cells. In this study, we found that 968 effectively inhibited NSCLC cell proliferation and migration and arrested G0/G1 phase of cell cycle...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28036268/role-of-vhl-hif1a-and-sdh-on-the-expression-of-mir-210-implications-for-tumoral-pseudo-hypoxic-fate
#18
Anna Merlo, Cristóbal Bernardo-Castiñeira, Inés Sáenz-de-Santa-María, Ana S Pitiot, Milagros Balbín, Aurora Astudillo, Nuria Valdés, Bartolomé Scola, Raquel Del Toro, Simón Méndez-Ferrer, José I Piruat, Carlos Suarez, María-Dolores Chiara
The hypoxia-inducible factor 1α (HIF-1α) and its microRNA target, miR-210, are candidate tumor-drivers of metabolic reprogramming in cancer. Neuroendocrine neoplasms such as paragangliomas (PGLs) are particularly appealing for understanding the cancer metabolic adjustments because of their associations with deregulations of metabolic enzymes, such as succinate dehydrogenase (SDH), and the von Hippel Lindau (VHL) gene involved in HIF-1α stabilization. However, the role of miR-210 in the pathogenesis of SDH-related tumors remains an unmet challenge...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28034771/lkb1-promotes-metabolic-flexibility-in-response-to-energy-stress
#19
Seth J Parker, Robert U Svensson, Ajit S Divakaruni, Austin E Lefebvre, Anne N Murphy, Reuben J Shaw, Christian M Metallo
The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using (13)C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1...
December 26, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/28030620/simulating-heterogeneous-tumor-cell-populations
#20
Andrew Sundstrom, Dafna Bar-Sagi, Bud Mishra
Certain tumor phenomena, like metabolic heterogeneity and local stable regions of chronic hypoxia, signify a tumor's resistance to therapy. Although recent research has shed light on the intracellular mechanisms of cancer metabolic reprogramming, little is known about how tumors become metabolically heterogeneous or chronically hypoxic, namely the initial conditions and spatiotemporal dynamics that drive these cell population conditions. To study these aspects, we developed a minimal, spatially-resolved simulation framework for modeling tissue-scale mixed populations of cells based on diffusible particles the cells consume and release, the concentrations of which determine their behavior in arbitrarily complex ways, and on stochastic reproduction...
2016: PloS One
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