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Warburg effect

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https://www.readbyqxmd.com/read/29229877/fermentative-metabolism-impedes-p53-dependent-apoptosis-in-a-crabtree-positive-but-not-in-crabtree-negative-yeast
#1
Abhay Kumar, Jaswandi Ujwal Dandekar, Paike Jayadeva Bhat
Tumour cells distinguish from normal cells by fermenting glucose to lactate in presence of sufficient oxygen and functional mitochondria (Warburg effect). Crabtree effect was invoked to explain the biochemical basis of Warburg effect by suggesting that excess glucose suppresses mitochondrial respiration. It is known that the Warburg effect and Crabtree effect are displayed by Saccharomyces cerevisiae, during growth on abundant glucose. Beyond this similarity, it was also demonstrated that expression of human pro-apoptotic proteins in S...
December 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/29229835/o-glcnacylation-destabilizes-the-active-tetrameric-pkm2-to-promote-the-warburg-effect
#2
Yang Wang, Jia Liu, Xin Jin, Dapeng Zhang, Dongxue Li, Fengqi Hao, Yunpeng Feng, Shan Gu, Fanlin Meng, Miaomiao Tian, Yi Zheng, Ling Xin, Xinbo Zhang, Xue Han, L Aravind, Min Wei
The Warburg effect, characterized by increased glucose uptake and lactate production, is a well-known universal across cancer cells and other proliferating cells. PKM2, a splice isoform of the pyruvate kinase (PK) specifically expressed in these cells, serves as a major regulator of this metabolic reprogramming with an adjustable activity subjected to numerous allosteric effectors and posttranslational modifications. Here, we have identified a posttranslational modification on PKM2, O-GlcNAcylation, which specifically targets Thr405 and Ser406, residues of the region encoded by the alternatively spliced exon 10 in cancer cells...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29228690/cartilage-oligomeric-matrix-protein-promotes-prostate-cancer-progression-by-enhancing-invasion-and-disrupting-intracellular-calcium-homeostasis
#3
Emelie Englund, Giacomo Canesin, Konstantinos S Papadakos, Neelanjan Vishnu, Emma Persson, Bart Reitsma, Aseem Anand, Laila Jacobsson, Leszek Helczynski, Hindrik Mulder, Anders Bjartell, Anna M Blom
Cartilage oligomeric matrix protein (COMP) was recently implicated in the progression of breast cancer. Immunostaining of 342 prostate cancer specimens in tissue microarrays showed that COMP expression is not breast cancer-specific but also occurs in prostate cancer. The expression of COMP in prostate cancer cells correlated with a more aggressive disease with faster recurrence. Subcutaneous xenografts in immunodeficient mice showed that the prostate cancer cell line DU145 overexpressing COMP formed larger tumors in vivo as compared to mock-transfected cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225125/interdependence-of-glo-i-and-pkm2-in-the-metabolic-shift-to-escape-apoptosis-in-glo-i-dependent-cancer-cells
#4
Nami Shimada, Ryoko Takasawa, Sei-Ichi Tanuma
Many cancer cells undergo metabolic reprogramming known as the Warburg effect, which is characterized by a greater dependence on glycolysis for ATP generation, even under normoxic conditions. Glyoxalase I (GLO I) is a rate-limiting enzyme involved in the detoxification of cytotoxic methylglyoxal formed in glycolysis and which is known to be highly expressed in many cancer cells. Thus, specific inhibitors of GLO I are expected to be effective anticancer drugs. We previously discovered a novel GLO I inhibitor named TLSC702...
December 7, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29224409/intellectual-property-considerations-for-molecular-diagnostic-development-with-emphasis-on-companion-diagnostics
#5
Harry Glorikian, Richard Jeremy Warburg, Kelly Moore, Jennifer Malinowski
The development of molecular diagnostics is a complex endeavor, with multiple regulatory pathways to consider and numerous approaches to development and commercialization. Companion diagnostics, devices which are "essential for the safe and effective use of a corresponding drug or diagnostic product" (see U.S. Food & Drug Administration, In Vitro Diagnostics - Companion Diagnostics, U.S. Dept. of Health & Human Services(2016), available at https://www.fda.gov/medicaldevices/productsandmedicalprocedures/invitrodiagnostics/ucm407297...
December 9, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29221144/ucp2-overexpression-enhanced-glycolysis-via-activation-of-pfkfb2-during-skin-cell-transformation
#6
Annapoorna Sreedhar, Petra Petruska, Sumitra Miriyala, Manikandan Panchatcharam, Yunfeng Zhao
Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane transporter which is often upregulated in human cancers. However, how this anion transporter affects tumorigenesis is not well understood. Using the skin cell transformation JB6 model, we demonstrated that UCP2 overexpression activated phosphofructokinase 2/fructose-2,6-bisphosphatase 2 (PFKFB2), a key regulator of glycolysis. In conjunction, upregulation of PFKFB2 expression correlated with elevated fructose 2,6-bisphosphate (Fru-2,6-P2) levels, 6-phosphofructo-1-kinase (PFK-1) activity, glucose uptake, and lactate production...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220380/hexokinase-2-hk2-the-tumor-promoter-in-glioma-is-downregulated-by-mir-218-bmi1-pathway
#7
Hui Liu, Nan Liu, Yingduan Cheng, Weilin Jin, Pengxing Zhang, Xin Wang, Hongwei Yang, Xiaoshan Xu, Zhen Wang, Yanyang Tu
In cancer, glycolysis driving enzymes and their regulating microRNAs are one of the key focus of oncology research lately. The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor. In the present study, we studied the tumorigenic role of HK2 in glioma, and clarified the mechanism of miR-218 induced HK2 regulation in glioma development. The HK2 expression in patient derived glioma and non neoplastic brain tissue was quantified. The HK2 silenced U87 and U251 cell lines were assessed for their proliferation, migration and invasive potential in vitro, while the tumor forming potential of U87 cells was evaluated in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/29218520/design-synthesis-and-evaluation-of-glut-inhibitors
#8
Carlotta Granchi, Tiziano Tuccinardi, Filippo Minutolo
The Warburg effect describes how most cancer cells exhibit higher-than-normal glucose consumption, not only under hypoxic conditions, but also when normal oxygen levels are present. Although glucose transporter 1 (GLUT1) has been found to play a key role in the cellular uptake of glucose, especially in cancer cells, where it is generally overexpressed, it has not been given consideration as a suitable target for the development of anticancer drugs. In this chapter, an example of molecular design and realization of novel GLUT1 inhibitors, including in silico modeling, chemical synthesis, and biological characterization, is provided...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29212305/cancer-energy-metabolism-shutting-power-off-cancer-factory
#9
REVIEW
Soo-Youl Kim
In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism...
December 7, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29212301/convergence-of-cancer-metabolism-and-immunity-an-overview
#10
REVIEW
Chi Van Dang, Jung-Whan Kim
Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells...
December 7, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29207896/rho-gtpase-effectors-and-nad-metabolism-in-cancer-immune-suppression
#11
Mahmoud Chaker, Audrey Minden, Suzie Chen, Robert H Weiss, Eduardo N Chini, Amit Mahipal, Asfar S Azmi
Sustained proliferative signaling and de-regulated cellular bioenergetics are two of the chief hallmarks of cancer. Alterations in the Ras pathway and its downstream effectors are among the major drivers for uncontrolled cell growth in many cancers. The GTPases are one of the signaling molecules that activate crucial signal transducing pathways downstream of Ras through several effector proteins. The GTPases (GTP bound) interact with several effectors and modulate a number of different biological pathways including those that regulate cytoskeleton, cellular motility, cytokinesis, proliferation, apoptosis, transcription and nuclear signaling...
December 6, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29207023/macrophage-migration-inhibitory-factor-promotes-warburg-effect-via-activation-of-the-nf%C3%A2-%C3%AE%C2%BAb-hif%C3%A2-1%C3%AE-pathway-in-lung-cancer
#12
Jun Li, Junhua Zhang, Fengjiao Xie, Jiangzhou Peng, Xu Wu
Macrophage migration inhibitory factor (MIF) is upregulated in various solid tumors, a process that is associated with tumor progression and metastasis. The present study aimed to investigate the role and the underlying mechanism of MIF in human lung cancer. Human lung cancer H358, H460, H524, H1650, H838, H1975 and A549 cell lines were used to examine the expression of MIF by real time‑quantitative polymerase chain reaction and western blotting. The lentivirus was used to overexpress MIF and the expression of MIF and hypoxia‑inducible factor 1‑α (HIF‑1α) were knocked down by shRNA or siRNA...
November 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29192176/pgc-1alpha-levels-correlate-with-survival-in-patients-with-stage-iii-nsclc-and-may-define-a-new-biomarker-to-metabolism-targeted-therapy
#13
Alberto Cruz-Bermúdez, Ramiro J Vicente-Blanco, Raquel Laza-Briviesca, Aránzazu García-Grande, Sara Laine-Menéndez, Lourdes Gutiérrez, Virginia Calvo, Atocha Romero, Paloma Martín-Acosta, José Miguel García, Mariano Provencio
Lung cancer remains the leading cause of cancer-related death worldwide, with one-third diagnosed with locally advanced (stage III) disease. Preoperative induction chemo-radiotherapy is key for the treatment of these patients, however conventional cisplatin based approaches has apparently reached a plateau of effectiveness. In the search for new therapies, the targeting of tumor metabolism is revealed as an interesting option to improve the patient's responses. Here we describe the importance of PGC-1alpha and GAPDH/MT-CO1 ratio levels as surrogates of the Warburg effect from a series of 28 stage III NSCLC patients, on PFS, OS and PET uptake...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29190547/low-folate-stress-reprograms-cancer-stem-cell-like-potentials-and-bioenergetics-metabolism-through-activation-of-mtor-signaling-pathway-to-promote-in-vitro-invasion-and-in-vivo-tumorigenicity-of-lung-cancers
#14
Wan-Jing Chen, Rwei-Fen S Huang
Low-folate (LF) nutritional status is associated with increased risks of lung cancer. It has unexplored effects on lung cancer malignancy, a cancer stem cell (CSC) disease. We hypothesized that LF may reprogram CSC-like potential and bioenergetics metabolism to increase metastasis potential of lung cancers. Cultivation of human non-small-cell lung cancer cells (H23) in an LF medium enhanced CSC-like properties signified by increased expressions of the CSC surface marker CD44 and pluripotency markers Sox2, Oct4 and ALDH1A1, and promoted self-renewal ability of anchorage-independent oncospheroid formation...
October 23, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29186898/thermodynamic-aspects-and-reprogramming-cellular-energy-metabolism-during-the-fibrosis-process
#15
REVIEW
Alexandre Vallée, Yves Lecarpentier, Jean-Noël Vallée
Fibrosis is characterized by fibroblast proliferation and fibroblast differentiation into myofibroblasts, which generate a relaxation-free contraction mechanism associated with excessive collagen synthesis in the extracellular matrix, which promotes irreversible tissue retraction evolving towards fibrosis. From a thermodynamic point of view, the mechanisms leading to fibrosis are irreversible processes that can occur through changing the entropy production rate. The thermodynamic behaviors of metabolic enzymes involved in fibrosis are modified by the dysregulation of both transforming growth factor β (TGF-β) signaling and the canonical WNT/β-catenin pathway, leading to aerobic glycolysis, called the Warburg effect...
November 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29165041/akt-mediated-phosphorylation-of-atg4b-impairs-mitochondrial-activity-and-enhances-the-warburg-effect-in-hepatocellular-carcinoma-cells
#16
Zhenhong Ni, Jintao He, Yaran Wu, Changjiang Hu, Xufang Dai, Xiaojing Yan, Bo Li, Xinzhe Li, Haojun Xiong, Yuming Li, Song Li, Liang Xu, Yongsheng Li, Jiqin Lian, Fengtian He
Phosphorylation is a major type of post-translational modification, which can influence the cellular physiological function. ATG4B, a key macroautophagy/autophagy-related protein, has a potential effect on the survival of tumor cells. However, it is still unknown as to the role of ATG4B phosphorylation in cancers. In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells. The phosphorylation of ATG4B at Ser34 had little effect on autophagic flux, but promoted the Warburg effect including the increase of L-lactate production and glucose consumption, and the decrease of oxygen consumption in HCC cells...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29162555/11%C3%AE-hydroxysteroid-dehydrogenase-1-deficiency-alters-brain-energy-metabolism-in-acute-systemic-inflammation
#17
Manu Verma, Tiina M J Kipari, Zhenguang Zhang, Tak Yung Man, Thorsten Forster, Natalie Z M Homer, Jonathan R Seckl, Megan C Holmes, Karen E Chapman
Chronically elevated glucocorticoid levels impair cognition and are pro-inflammatory in the brain. Deficiency or inhibition of 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), which converts inactive into active glucocorticoids, protects against glucocorticoid-associated chronic stress- or age-related cognitive impairment. Here, we hypothesised that 11β-HSD1 deficiency attenuates the brain cytokine response to inflammation. Because inflammation is associated with altered energy metabolism, we also examined the effects of 11β-HSD1 deficiency upon hippocampal energy metabolism...
November 21, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29161787/cancer-control-algorithm
#18
Sunil Kumar Kashyap, Birendra Kumar Sharma, Amitabh Banerjee
Curing cancer by controlling the growth of the cancer cell is the objective of this paper. The growth of the cancer cell is analysed by the optimization programming. The algorithm is proposed for minimizing the rate of growth of the cancer cell. Hence the chaotic cancer became structured for the further research. This is an extended work of Warburg [1], where he defined the centre of the cancer cell, known by Warburg effect, but here we control the increasing radius of the cancer circle by the proposed Cancer Control Algorithm...
November 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/29160745/the-unveiling-of-the-warburg-effect-and-the-inscribed-innovative-approach-to-a-radical-non-toxic-anticancer-therapy
#19
Olivia Crociani, Ilaria Marzi, Maria Grazia Cipolleschi, Antonella Mannini, Massimo Contini, Massimo Olivotto
The purpose of this research has been deciphering the Warburg paradox, the biochemical enigma unsolved since 1923. This paradox consists of the aerobic pyruvate conversion to lactate brought about by anaplastic cancer, through the metabolic pathway known as aerobic glycolysis. This pathway implies a heavy energetic waste. We solved the enigma by demonstrating that its specific character, i.e. the forced aerobic lactate exportation, represents a crucial metabolic device to counteract the cytotoxic effect produced by an excess of pyruvate at the connection of glycolysis with the Krebs cycle...
November 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29156694/pdac-derived-exosomes-enrich-the-microenvironment-in-mdscs-in-a-smad4-dependent-manner-through-a-new-calcium-related-axis
#20
Daniela Basso, Elisa Gnatta, Andrea Padoan, Paola Fogar, Sara Furlanello, Ada Aita, Dania Bozzato, Carlo-Federico Zambon, Giorgio Arrigoni, Chiara Frasson, Cinzia Franchin, Stefania Moz, Thomas Brefort, Thomas Laufer, Filippo Navaglia, Sergio Pedrazzoli, Giuseppe Basso, Mario Plebani
Tumor genetics and escape from immune surveillance concur in the poor prognosis of PDAC. In this study an experimental model was set up to verify whether SMAD4, deleted in about 55% PDAC and associated with poor prognosis, is involved in determining immunosuppression through Exosomes (Exo). Potential mechanisms and mediators underlying SMAD4-dependent immunosuppression were evaluated by studying intracellular calcium (Fluo-4), Exo-miRNAs (microarray) and Exo-proteins (SILAC). Two PDAC cell lines expressing (BxPC3-SMAD4+) or not-expressing (BxPC3) SMAD4 were used to prepare Exo-enriched conditioned media, employed in experiments with blood donors PBMCs...
October 17, 2017: Oncotarget
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