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Warburg effect

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https://www.readbyqxmd.com/read/28230866/oridonin-induces-autophagy-via-inhibition-of-glucose-metabolism-in-p53-mutated-colorectal-cancer-cells
#1
Zhuo Yao, Fuhua Xie, Min Li, Zirui Liang, Wenli Xu, Jianhua Yang, Chang Liu, Hongwangwang Li, Hui Zhou, Liang-Hu Qu
The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28228400/inhibiting-aerobic-glycolysis-suppresses-renal-interstitial-fibroblasts-activation-and-renal-fibrosis
#2
Hao Ding, Lei Jiang, Jing Xu, Feng Bai, Yang Zhou, Qi Yuan, Jing Luo, Ke Zen, Junwei Yang
Chronic kidney diseases (CKD) generally lead to renal fibrosis. Despite great progresses have been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear and so far no effective therapeutic anti-fibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis, and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28218905/phosphorylation-mediated-activation-of-ldha-promotes-cancer-cell-invasion-and-tumour-metastasis
#3
L Jin, J Chun, C Pan, G N Alesi, D Li, K R Magliocca, Y Kang, Z G Chen, D M Shin, F R Khuri, J Fan, S Kang
Metastases remain the major cause of death from cancer. Recent molecular advances have highlighted the importance of metabolic alterations in cancer cells, including the Warburg effect that describes an increased glycolysis in cancer cells. However, how this altered metabolism contributes to tumour metastasis remains elusive. Here, we report that phosphorylation-induced activation of lactate dehydrogenase A (LDHA), an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28216603/use-of-mature-mirna-strand-selection-in-mirnas-families-in-cervical-cancer-development
#4
REVIEW
Angelica Judith Granados-López, José Luis Ruiz-Carrillo, Luis Steven Servín-González, José Luis Martínez-Rodríguez, Claudia Araceli Reyes-Estrada, Rosalinda Gutiérrez-Hernández, Jesús Adrián López
Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt) chain sizes...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28202516/modeling-the-genetic-regulation-of-cancer-metabolism-interplay-between-glycolysis-and-oxidative-phosphorylation
#5
Linglin Yu, Mingyang Lu, Dongya Jia, Jianpeng Ma, Eshel Ben-Jacob, Herbert Levine, Benny A Kaipparettu, Jose' N Onuchic
Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and OXPHOS. Integrating information from literature, we constructed a regulatory network of genes and metabolites from which we extracted a core circuit containing HIF-1, AMPK, and ROS...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197395/characterization-of-the-tumor-microenvironment-and-tumor-stroma-interaction-by-non-invasive-preclinical-imaging
#6
REVIEW
Nirilanto Ramamonjisoa, Ellen Ackerstaff
Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28196867/synaptic-activity-drives-a-genomic-program-that-promotes-a-neuronal-warburg-effect
#7
Carlos Bas-Orth, Yan-Wei Tan, David Lau, Hilmar Bading
Synaptic activity drives changes in gene expression to promote long-lasting adaptations of neuronal structure and function. One example of such an adaptive response is the buildup of acquired neuroprotection, a synaptic activity- and gene transcription-mediated increase in the resistance of neurons against harmful conditions. A hallmark of acquired neuroprotection is the stabilization of mitochondrial structure and function. We therefore re-examined previously identified sets of synaptic activity-regulated genes to identify genes that are directly linked to mitochondrial function...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28194038/itd-mutation-in-flt3-tyrosine-kinase-promotes-warburg-effect-and-renders-therapeutic-sensitivity-to-glycolytic-inhibition
#8
H-Q Ju, G Zhan, A Huang, Y Sun, S Wen, J Yang, W-H Lu, R-H Xu, J Li, Y Li, G Garcia-Manero, P Huang, Y Hu
Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28184935/involvement-of-ezh2-in-aerobic-glycolysis-of-prostate-cancer-through-mir-181b-hk2-axis
#9
Tao Tao, Ming Chen, Ranran Jiang, Han Guan, Yeqing Huang, Huan Su, Qiang Hu, Xu Han, Jun Xiao
Recent studies suggest that several types of tumors preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. However, it remains largely unexplored whether metabolic reprogramming is involved in prostate cancer (PCa) progression. In this study, we found that histone methyltransferase enhancer of zeste homolog 2 (EZH2) dysregulated in PCa development regulated cellular growth and aerobic glycolysis through miR-181b/hexokinase 2 (HK2) axis. Aberrant expression profiles of coding RNA and microRNA were examined by two large, independent clinical prostate cancer data sets...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28183841/mathematical-modeling-links-wnt-signaling-to-emergent-patterns-of-metabolism-in-colon-cancer
#10
Mary Lee, George T Chen, Eric Puttock, Kehui Wang, Robert A Edwards, Marian L Waterman, John Lowengrub
Cell-intrinsic metabolic reprogramming is a hallmark of cancer that provides anabolic support to cell proliferation. How reprogramming influences tumor heterogeneity or drug sensitivities is not well understood. Here, we report a self-organizing spatial pattern of glycolysis in xenograft colon tumors where pyruvate dehydrogenase kinase (PDK1), a negative regulator of oxidative phosphorylation, is highly active in clusters of cells arranged in a spotted array. To understand this pattern, we developed a reaction-diffusion model that incorporates Wnt signaling, a pathway known to upregulate PDK1 and Warburg metabolism...
February 9, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28179591/correction-mtdna-depleted-pc3-cells-exhibit-warburg-effect-and-cancer-stem-cell-features
#11
Xiaoran Li, Yali Zhong, Jie Lu, Karol Axcrona, Lars Eide, Randi G Syljuåsen, Qian Peng, Junbai Wang, Hongquan Zhang, Mariusz Adam Goscinski, Gunnar Kvalheim, Jahn M Nesland, Zhenhe Suo
No abstract text is available yet for this article.
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28173837/insulin-like-growth-factor-1-receptor-activation-promotes-mammary-gland-tumor-development-by-increasing-glycolysis-and-promoting-biomass-production
#12
Bas Ter Braak, Christine L Siezen, Joo S Lee, Pooja Rao, Charlotte Voorhoeve, Eytan Ruppin, Jan Willem van der Laan, Bob van de Water
BACKGROUND: The insulin-like growth factor 1 (IGF1) signaling axis plays a major role in tumorigenesis. In a previous experiment, we chronically treated mice with several agonists of the IGF1 receptor (IGF1R). We found that chronic treatment with insulin analogues with high affinity towards the IGF1R (IGF1 and X10) decreased the mammary gland tumor latency time in a p53(R270H/+)WAPCre mouse model. Frequent injections with insulin analogues that only mildly activated the IGF1R in vivo (glargine and insulin) did not significantly decrease the tumor latency time in this mouse model...
February 7, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28168164/vdac-tubulin-an-anti-warburg-pro-oxidant-switch
#13
REVIEW
Eduardo N Maldonado
Aerobic enhanced glycolysis characterizes the Warburg phenotype. In cancer cells, suppression of mitochondrial metabolism contributes to maintain a low ATP/ADP ratio that favors glycolysis. We propose that the voltage-dependent anion channel (VDAC) located in the mitochondrial outer membrane is a metabolic link between glycolysis and oxidative phosphorylation in the Warburg phenotype. Most metabolites including respiratory substrates, ADP, and Pi enter mitochondria only through VDAC. Oxidation of respiratory substrates in the Krebs cycle generates NADH that enters the electron transport chain (ETC) to generate a proton motive force utilized to generate ATP and to maintain mitochondrial membrane potential (ΔΨ)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28167100/cancer-metabolism-in-space-and-time-beyond-the-warburg-effect
#14
Pierre Danhier, Piotr Bański, Valéry L Payen, Debora Grasso, Luigi Ippolito, Pierre Sonveaux, Paolo E Porporato
Altered metabolism in cancer cells is pivotal for tumor growth, most notably by providing energy, reducing equivalents and building blocks while several metabolites exert a signaling function promoting tumor growth and progression. A cancer tissue cannot be simply reduced to a bulk of proliferating cells. Tumors are indeed complex and dynamic structures where single cells can heterogeneously perform various biological activities with different metabolic requirements. Because tumors are composed of different types of cells with metabolic activities affected by different spatial and temporal contexts, it is important to address metabolism taking into account cellular and biological heterogeneity...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28143530/a-first-immunohistochemistry-study-of-transketolase-and-transketolase-like-1-expression-in-canine-hyperplastic-and-neoplastic-mammary-lesions
#15
Giovanni Pietro Burrai, Alessandro Tanca, Tiziana Cubeddu, Marcello Abbondio, Marta Polinas, Maria Filippa Addis, Elisabetta Antuofermo
BACKGROUND: Canine mammary tumors represent the most common neoplasm in female dogs, and the discovery of cancer biomarkers and their translation to clinical relevant assays is a key requirement in the war on cancer. Since the description of the 'Warburg effect', the reprogramming of metabolic pathways is considered a hallmark of pathological changes in cancer cells. In this study, we investigate the expression of two cancer-related metabolic enzymes, transketolase (TKT) and transketolase-like 1 (TKTL1), involved in the pentose phosphate pathway (PPP), an alternative metabolic pathway for glucose breakdown that could promote cancer by providing the precursors and energy required for rapidly growing cells...
January 31, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28134810/acidosis-activates-endoplasmic-reticulum-stress-pathways-through-gpr4-in-human-vascular-endothelial-cells
#16
Lixue Dong, Elizabeth A Krewson, Li V Yang
Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the "Warburg effect"), and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined...
January 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28125711/monitoring-mitochondrial-complex-i-activity-using-novel-pet-probe-18f-bcpp-ef-allows-early-detection-of-radiotherapy-effect-in-murine-squamous-cell-carcinoma
#17
Chieko Murayama, Akira T Kawaguchi, Akemi Kamijo, Katsuko Naito, Masakatsu Kanazawa, Hideo Tsukada
OBJECTIVES: Aerobic glycolysis, the main pathway of energy production in tumors (Warburg effect) allows detection of tumors by positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (18F-FDG). Since ionizing radiation (IR) is reported to switch aerobic glycolysis to mitochondrial oxidative phosphorylation, radiotherapeutic efficacy was monitored by the activity of mitochondrial complex I (MC-I), using a new PET probe 18F-BCPP-EF, 18F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoro-ethoxy)-ethoxy] -pyridine-3-ylmethoxy}-2H-pyridazin-3-one, compared with 18F-FDG uptake and the apoptosis index...
2017: PloS One
https://www.readbyqxmd.com/read/28122260/out-of-warburg-effect-an-effective-cancer-treatment-targeting-the-tumor-specific-metabolism-and-dysregulated-ph
#18
REVIEW
Laurent Schwartz, Thomas Seyfried, Khalid O Alfarouk, Jorgelindo Da Veiga Moreira, Stefano Fais
As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models...
January 22, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28122247/arginine-deprivation-inhibits-the-warburg-effect-and-upregulates-glutamine-anaplerosis-and-serine-biosynthesis-in-ass1-deficient-cancers
#19
Jeff Charles Kremer, Bethany Cheree Prudner, Sara Elaine Stubbs Lange, Gregory Richard Bean, Matthew Bailey Schultze, Caitlyn Brook Brashears, Megan DeAnna Radyk, Nathan Redlich, Shin-Cheng Tzeng, Kenjiro Kami, Laura Shelton, Aixiao Li, Zack Morgan, John Stephen Bomalaski, Takashi Tsukamoto, Jon McConathy, Loren Scott Michel, Jason Matthew Held, Brian Andrew Van Tine
Targeting defects in metabolism is an underutilized strategy for the treatment of cancer. Arginine auxotrophy resulting from the silencing of argininosuccinate synthetase 1 (ASS1) is a common metabolic alteration reported in a broad range of aggressive cancers. To assess the metabolic effects that arise from acute and chronic arginine starvation in ASS1-deficient cell lines, we performed metabolite profiling. We found that pharmacologically induced arginine depletion causes increased serine biosynthesis, glutamine anaplerosis, oxidative phosphorylation, and decreased aerobic glycolysis, effectively inhibiting the Warburg effect...
January 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/28120890/systems-biology-analysis-of-drivers-underlying-hallmarks-of-cancer-cell-metabolism
#20
Daniel C Zielinski, Neema Jamshidi, Austin J Corbett, Aarash Bordbar, Alex Thomas, Bernhard O Palsson
Malignant transformation is often accompanied by significant metabolic changes. To identify drivers underlying these changes, we calculated metabolic flux states for the NCI60 cell line collection and correlated the variance between metabolic states of these lines with their other properties. The analysis revealed a remarkably consistent structure underlying high flux metabolism. The three primary uptake pathways, glucose, glutamine and serine, are each characterized by three features: (1) metabolite uptake sufficient for the stoichiometric requirement to sustain observed growth, (2) overflow metabolism, which scales with excess nutrient uptake over the basal growth requirement, and (3) redox production, which also scales with nutrient uptake but greatly exceeds the requirement for growth...
January 25, 2017: Scientific Reports
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