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Warburg effect

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https://www.readbyqxmd.com/read/28325773/cue-domain-containing-protein-2-promotes-the-warburg-effect-and-tumorigenesis
#1
Xiuying Zhong, Shengya Tian, Xiang Zhang, Xinwei Diao, Fangting Dong, Jie Yang, Zhaoyong Li, Linchong Sun, Lin Wang, Xiaoping He, Gongwei Wu, Xin Hu, Lihua Wang, Libing Song, Huafeng Zhang, Xin Pan, Ailing Li, Ping Gao
Cancer progression depends on cellular metabolic reprogramming as both direct and indirect consequence of oncogenic lesions; however, the underlying mechanisms are still poorly understood. Here, we report that CUEDC2 (CUE domain-containing protein 2) plays a vital role in facilitating aerobic glycolysis, or Warburg effect, in cancer cells. Mechanistically, we show that CUEDC2 upregulates the two key glycolytic proteins GLUT3 and LDHA via interacting with the glucocorticoid receptor (GR) or 14-3-3ζ, respectively...
March 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28325264/role-of-ketogenic-metabolic-therapy-in-malignant-glioma-a-systematic-review
#2
REVIEW
Sebastian F Winter, Franziska Loebel, Jorg Dietrich
BACKGROUND: Coined as the "Warburg effect" and a recognized hallmark of cancer, energy metabolism is aberrantly geared towards aerobic glycolysis in most human cancers, including malignant glioma. Ketogenic metabolic therapy (KMT), i.e. nutritional intervention with ketogenic or low-glycemic diets, has been proposed as an anti-neoplastic strategy in glioma patients. MATERIALS AND METHODS: We here review the rationale and existing data investigating KMT in management of patients with malignant glioma and discuss the promise and potential challenges of this novel strategy...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28321489/microrna-regulation-and-analytical-methods-in-cancer-cell-metabolism
#3
REVIEW
Ling-Fei Zhang, Shuai Jiang, Mo-Fang Liu
The reprogramming of glucose metabolism from oxidative to glycolytic metabolism, known as the Warburg effect, is an anomalous characteristic of cancer cell metabolism. Recent studies have revealed a subset of microRNAs (miRNAs) that play critical roles in regulating the reprogramming of glucose metabolism in cancer cells. These miRNAs regulate cellular glucose metabolism by directly targeting multiple metabolic genes, including those encoding key glycolytic enzymes. In the first part of this review, we summarized the recent knowledge of miRNA regulation in the reprogramming of glucose metabolism in cancer cells and discussed the potential utilization of the key miRNA regulators as metabolic targets for developing new antitumor agents...
March 20, 2017: Cellular and Molecular Life Sciences: CMLS
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/28314935/a-disease-with-a-sweet-tooth-exploring-the-warburg-effect-in-alzheimer-s-disease
#5
REVIEW
Anna Atlante, Lidia de Bari, Antonella Bobba, Giuseppina Amadoro
After more than 80 years from the revolutionary discoveries of Otto Warburg, who observed high glucose dependency, with increased glycolysis and lactate production regardless of oxygen availability in most cancer cells, the 'Warburg effect' returns to the fore in neuronal cells affected by Alzheimer's disease (AD). Indeed, it seems that, in the mild phase of AD, neuronal cells "prefer" to use the energetically inefficient method of burning glucose by glycolysis, as in cancer, proving to become resistant to β-amyloid (Aβ)-dependent apoptosis...
March 17, 2017: Biogerontology
https://www.readbyqxmd.com/read/28314283/stable-shrna-silencing-of-lactate-dehydrogenase-a-ldha-in-human-mda-mb-231-breast-cancer-cells-fails-to-alter-lactic-acid-production-glycolytic-activity-atp-or-survival
#6
Nzinga Mack, Elizabeth A Mazzio, David Bauer, Hernan Flores-Rozas, Karam F A Soliman
BACKGROUND: In the US, African Americans have a high death rate from triple-negative breast cancer (TNBC), characterized by lack of hormone receptors (ER, PR, HER2/ERRB2) which are otherwise valuable targets of chemotherapy. There is a need to identify novel targets that negatively impact TNBC tumorigenesis. TNBCs release an abundance of lactic acid, under normoxic, hypoxic and hyperoxic conditions; this referred to as the Warburg effect. Accumulated lactic acid sustains peri-cellular acidity which propels metastatic invasion and malignant aggressive transformation...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28298922/interactions-between-ppar-gamma-and-the-canonical-wnt-beta-catenin-pathway-in-type-2-diabetes-and-colon-cancer
#7
REVIEW
Yves Lecarpentier, Victor Claes, Alexandre Vallée, Jean-Louis Hébert
In both colon cancer and type 2 diabetes, metabolic changes induced by upregulation of the Wnt/beta-catenin signaling and downregulation of peroxisome proliferator-activated receptor gamma (PPAR gamma) may help account for the frequent association of these two diseases. In both diseases, PPAR gamma is downregulated while the canonical Wnt/beta-catenin pathway is upregulated. In colon cancer, upregulation of the canonical Wnt system induces activation of pyruvate dehydrogenase kinase and deactivation of the pyruvate dehydrogenase complex...
2017: PPAR Research
https://www.readbyqxmd.com/read/28298645/role-for-the-atpase-inhibitory-factor-1-in-the-environmental-carcinogen-induced-warburg-phenotype
#8
Kévin Hardonnière, Morgane Fernier, Isabelle Gallais, Baharia Mograbi, Normand Podechard, Eric Le Ferrec, Nathalie Grova, Brice Appenzeller, Agnès Burel, Martine Chevanne, Odile Sergent, Laurence Huc, Sylvie Bortoli, Dominique Lagadic-Gossmann
Most tumors undergo metabolic reprogramming towards glycolysis, the so-called Warburg effect, to support growth and survival. Overexpression of IF1, the physiological inhibitor of the F0F1ATPase, has been related to this phenomenon and appears to be a relevant marker in cancer. Environmental contributions to cancer development are now widely accepted but little is known about the underlying intracellular mechanisms. Among the environmental pollutants humans are commonly exposed to, benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons (PAHs), is a well-known human carcinogen...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28288137/manganese-superoxide-dismutase-deficiency-triggers-mitochondrial-uncoupling-and-the-warburg-effect
#9
Y Xu, S Miriyala, F Fang, V Bakthavatchalu, T Noel, D M Schnell, C Wang, W H St Clair, D K St Clair
No abstract text is available yet for this article.
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28284719/hypoxia-mediated-mechanisms-associated-with-antiangiogenic-treatment-resistance-in-glioblastomas
#10
REVIEW
Sean Mahase, Rachel N Rattenni, Pieter Wesseling, William Leenders, Clarissa Baldotto, Rajan Jain, David Zagzag
Glioblastomas (GBMs) are malignant tumors characterized by their vascularity and invasive capabilities. Antiangiogenic therapy (AAT) is a treatment option that targets GBM-associated vasculature to mitigate the growth of GBMs. However, AAT demonstrates transient effects, because many patients eventually develop resistance to this treatment. Several recent studies attempt to explain the molecular and biochemical basis of resistance to AAT in GBM patients. Experimental investigations suggest that the induction of extensive intratumoral hypoxia plays a key role in GBM escape from AAT...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28281102/glutamine-addiction-in-gliomas
#11
Javier Márquez, Francisco J Alonso, José M Matés, Juan A Segura, Mercedes Martín-Rufián, José A Campos-Sandoval
Cancer cells develop and succeed by shifting to different metabolic programs compared with their normal cell counterparts. One of the classical hallmarks of cancer cells is their higher glycolysis rate and lactate production even in the presence of abundant O2 (Warburg effect). Another common metabolic feature of cancer cells is a high rate of glutamine (Gln) consumption normally exceeding their biosynthetic and energetic needs. The term Gln addiction is now widely used to reflect the strong dependence shown by most cancer cells for this essential nitrogen substrate after metabolic reprogramming...
March 9, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28270511/quantifying-intracellular-rates-of-glycolytic-and-oxidative-atp-production-and-consumption-using-extracellular-flux-measurements
#12
Shona A Mookerjee, Akos A Gerencser, David G Nicholls, Martin D Brand
Partitioning of ATP generation between glycolysis and oxidative phosphorylation is central to cellular bioenergetics but cumbersome to measure. We describe here how rates of ATP generation by each pathway can be calculated from simultaneous measurements of extracellular acidification and oxygen consumption. We update theoretical maximum ATP yields by mitochondria and cells catabolizing differ- ent substrates. Mitochondrial P/O ratios are 2.73 for oxidation of pyruvate plus malate and 1.64 for oxidation of succinate...
March 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28267743/a-large-scale-targeted-proteomics-assay-resource-based-on-an-in-vitro-human-proteome
#13
Masaki Matsumoto, Fumiko Matsuzaki, Kiyotaka Oshikawa, Naoki Goshima, Masatoshi Mori, Yoshifumi Kawamura, Koji Ogawa, Eriko Fukuda, Hirokazu Nakatsumi, Tohru Natsume, Kazuhiko Fukui, Katsuhisa Horimoto, Takeshi Nagashima, Ryo Funayama, Keiko Nakayama, Keiichi I Nakayama
Targeted proteomics approaches are of value for deep and accurate quantification of protein abundance. Extending such methods to quantify large numbers of proteins requires the construction of predefined targeted assays. We developed a targeted proteomics platform-in vitro proteome-assisted multiple reaction monitoring (MRM) for protein absolute quantification (iMPAQT)-by using >18,000 human recombinant proteins, thus enabling protein absolute quantification on a genome-wide scale. Our platform comprises experimentally confirmed MRM assays of mass tag (mTRAQ)-labeled peptides to allow for rapid and straightforward measurement of the absolute abundance of predefined sets of proteins by mass spectrometry...
March 2017: Nature Methods
https://www.readbyqxmd.com/read/28267240/integrated-functions-of-membrane-type-1-matrix-metalloproteinase-in-regulating-cancer-malignancy-beyond-a-proteinase
#14
REVIEW
Takeharu Sakamoto, Motoharu Seiki
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed in different types of invasive and proliferative cells, including cancer cells and stromal cells. MT1-MMP cleaves extracellular matrix proteins, membrane proteins, and other pericellular proteins, thereby changing the cellular microenvironment and regulating signal activation. Critical roles of protease activity in cancer cell proliferation, invasion, and metastasis have been demonstrated by many groups. MT1-MMP also has a non-protease activity in that it inhibits the oxygen-dependent suppression of hypoxia-inducible factors (HIFs) via Munc18-1-interacting protein 3 (Mint3) and thereby enhances the expression of HIF target genes...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28263181/the-cancer-warburg-effect-may-be-a-testable-example-of-the-minimum-entropy-production-rate-principle
#15
Bartolome Sabater, Dolores Marin
Cancer cells consume more glucose by glycolytic fermentation to lactate than by respiration, a characteristic known as the Warburg effect. In contrast with the 34 moles of ATP produced by respiration, fermentation produces two moles of ATP per mole of glucose consumed, which poses a puzzle on the function of the Warburg effect. Productions of free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) per mole linearly vary with the fraction (x) of glucose consumed by fermentation that is frequently estimated around 0...
March 6, 2017: Physical Biology
https://www.readbyqxmd.com/read/28262837/inhibiting-histone-deacetylases-suppresses-glucose-metabolism-and-hepatocellular-carcinoma-growth-by-restoring-fbp1-expression
#16
Jing Yang, Xin Jin, Yuqian Yan, Yingjie Shao, Yunqian Pan, Lewis R Roberts, Jun Zhang, Haojie Huang, Jingting Jiang
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers in the world. Elevated glucose metabolism in the availability of oxygen, a phenomenon called the Warburg effect, is important for cancer cell growth. Fructose-1,6-bisphosphatase (FBP1) is a rate-limiting enzyme in gluconeogenesis and is frequently lost in various types of cancer. Here, we demonstrated that expression of FBP1 was downregulated in HCC patient specimens and decreased expression of FBP1 associated with poor prognosis. Low expression of FBP1 correlated with high levels of histone deacetylase 1 (HDAC1) and HDAC2 proteins in HCC patient tissues...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261475/the-action-of-%C3%AE-hydroxybutyrate-on-the-growth-metabolism-and-global-histone-h3-acetylation-of-spontaneous-mouse-mammary-tumours-evidence-of-a-%C3%AE-hydroxybutyrate-paradox
#17
Loreta M Rodrigues, Santiago Uribe-Lewis, Basetti Madhu, Davina J Honess, Marion Stubbs, John R Griffiths
BACKGROUND: Ketone bodies have both metabolic and epigenetic roles in cancer. In several studies, they showed an anti-cancer effect via inhibition of histone deacetylases; however, other studies observed faster tumour growth. The related molecule butyrate also inhibits growth of some cancer cells and accelerates it in others. This "butyrate paradox" is thought to be due to butyrate mediating histone acetylation and thus inhibiting cell proliferation in cancers that preferentially utilise glucose (the Warburg effect); whereas in cells that oxidise butyrate as a fuel, it fails to reach inhibitory concentrations and can stimulate growth...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/28258651/nmr-metabolomics-highlights-sphingosine-kinase-1-as-a-new-molecular-switch-in-the-orchestration-of-aberrant-metabolic-phenotype-in-cancer-cells
#18
Caterina Bernacchioni, Veronica Ghini, Francesca Cencetti, Lukasz Japtok, Chiara Donati, Paola Bruni, Paola Turano
Strong experimental evidence in animal and cellular models supports a pivotal role of sphingosine kinase (SK) 1 in oncogenesis. In many human cancers, SK1 levels are upregulated and these increases are linked to poor prognosis in patients. Here, by employing untargeted NMR-based metabolomic profiling combined with functional validations, we report the crucial role of SK1 in the metabolic shift known as the Warburg effect in A2780 ovarian cancer cells. Indeed, expression of SK1 induced a high glycolytic rate, characterized by increased levels of lactate along with increased expression of the proton/monocarboxylate symporter MCT1, and decreased oxidative metabolism, associated with the accumulation of intermediates of the tricarboxylic acid cycle and reduction of CO2 production...
March 4, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28245921/a-gradient-of-glycolytic-activity-coordinates-fgf-and-wnt-signaling-during-elongation-of-the-body-axis-in-amniote-embryos
#19
Masayuki Oginuma, Philippe Moncuquet, Fengzhu Xiong, Edward Karoly, Jérome Chal, Karine Guevorkian, Olivier Pourquié
Mammalian embryos transiently exhibit aerobic glycolysis (Warburg effect), a metabolic adaptation also observed in cancer cells. The role of this particular type of metabolism during vertebrate organogenesis is currently unknown. Here, we provide evidence for spatiotemporal regulation of glycolysis in the posterior region of mouse and chicken embryos. We show that a posterior glycolytic gradient is established in response to graded transcription of glycolytic enzymes downstream of fibroblast growth factor (FGF) signaling...
February 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28241470/pancreatic-exocrine-insufficiency-in-pancreatic-cancer
#20
REVIEW
Miroslav Vujasinovic, Roberto Valente, Marco Del Chiaro, Johan Permert, J-Matthias Löhr
Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion...
February 23, 2017: Nutrients
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