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Warburg effect cancer

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https://www.readbyqxmd.com/read/28922380/the-warburg-effect-as-an-adaptation-of-cancer-cells-to-rapid-fluctuations-in-energy-demand
#1
Tamir Epstein, Robert A Gatenby, Joel S Brown
To maintain optimal fitness, a cell must balance the risk of inadequate energy reserve for response to a potentially fatal perturbation against the long-term cost of maintaining high concentrations of ATP to meet occasional spikes in demand. Here we apply a game theoretic approach to address the dynamics of energy production and expenditure in eukaryotic cells. Conventionally, glucose metabolism is viewed as a function of oxygen concentrations in which the more efficient oxidation of glucose to CO2 and H2O produces all or nearly all ATP except under hypoxic conditions when less efficient (2 ATP/ glucose vs...
2017: PloS One
https://www.readbyqxmd.com/read/28918937/a-predictive-model-for-selective-targeting-of-the-warburg-effect-through-gapdh-inhibition-with-a-natural-product
#2
Maria V Liberti, Ziwei Dai, Suzanne E Wardell, Joshua A Baccile, Xiaojing Liu, Xia Gao, Robert Baldi, Mahya Mehrmohamadi, Marc O Johnson, Neel S Madhukar, Alexander A Shestov, Iok I Christine Chio, Olivier Elemento, Jeffrey C Rathmell, Frank C Schroeder, Donald P McDonnell, Jason W Locasale
Targeted cancer therapies that use genetics are successful, but principles for selectively targeting tumor metabolism that is also dependent on the environment remain unknown. We now show that differences in rate-controlling enzymes during the Warburg effect (WE), the most prominent hallmark of cancer cell metabolism, can be used to predict a response to targeting glucose metabolism. We establish a natural product, koningic acid (KA), to be a selective inhibitor of GAPDH, an enzyme we characterize to have differential control properties over metabolism during the WE...
September 8, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28915713/the-reverse-warburg-effect-is-likely-to-be-an-achilles-heel-of-cancer-that-can-be-exploited-for-cancer-therapy
#3
REVIEW
Yaojie Fu, Shanshan Liu, Shanghelin Yin, Weihong Niu, Wei Xiong, Ming Tan, Guiyuan Li, Ming Zhou
Although survival outcomes of cancer patients have been improved dramatically via conventional chemotherapy and targeted therapy over the last decades, there are still some tough clinical challenges that badly needs to be overcome, such as anticancer drug resistance, inevitable recurrences, cancer progression and metastasis. Simultaneously, accumulated evidence demonstrates that aberrant glucose metabolism termed 'the Warburg effect' in cancer cell is closely associated with malignant phenotypes. In 2009, a novel 'two-compartment metabolic coupling' model, also named 'the reverse Warburg effect', was proposed and attracted lots of attention...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915394/overcoming-the-warburg-effect-is-it-the-key-to-survival-in-sepsis
#4
REVIEW
David Bar-Or, Matthew Carrick, Allen Tanner, Mark J Lieser, Leonard T Rael, Edward Brody
Sepsis is a leading cause of mortality in the U.S. and Europe. Sepsis and septic shock are the results of severe metabolic abnormalities following infection. Aerobic glycolysis (the Warburg Effect) is as much a hallmark of sepsis as it is of cancer. Warburg observed that cancer cells generated energy through glycolysis (generation of ATP through degradation of glucose, usually associated with anaerobic conditions) rather than through oxidative phosphorylation (generation of ATP through the mitochondrial inner membrane via the tricarboxylic acid cycle, usually associated with aerobic conditions)...
September 8, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28914667/metabolic-regulation-of-macrophages-in-tumor-microenvironment
#5
Jaehong Kim, Jong-Sup Bae
PURPOSE OF REVIEW: Insight into the metabolic changes in cancer has become so important that cancer is regarded as a disease entity full of metabolic implications. We summarize the recent findings pertaining to cancer cell-derived metabolic changes that regulate the function of macrophages to favor cancer cell survival, and the reported approaches to reverse these changes. RECENT FINDINGS: Since the observation and dramatic revitalization of the Warburg effect, metabolic changes were thought to be confined in cancer cells...
September 13, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28903423/mitochondria-sustain-store-operated-currents-in-colon-cancer-cells-but-not-in-normal-colonic-cells-reversal-by-non-steroidal-anti-inflammatory-drugs
#6
Miriam Hernández-Morales, Diego Sobradillo, Ruth A Valero, Eva Muñoz, Daniel Ubierna, Mary P Moyer, Lucía Núñez, Carlos Villalobos
Tumor cells undergo a critical remodeling of intracellular Ca(2+) homeostasis that contribute to important cancer hallmarks. Store-operated Ca(2+) entry (SOCE), a Ca(2+) entry pathway modulated by mitochondria, is dramatically enhanced in colon cancer cells. In addition, most cancer cells display the Warburg effect, a metabolic switch from mitochondrial metabolism to glycolysis that provides survival advantages. Accordingly, we investigated mitochondria control of store-operated currents (SOCs) in two cell lines previously selected for representing human normal colonic cells and colon cancer cells...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900510/egln1-c-myc-induced-lymphoid-specific-helicase-inhibits-ferroptosis-through-lipid-metabolic-gene-expression-changes
#7
Yiqun Jiang, Chao Mao, Rui Yang, Bin Yan, Ying Shi, Xiaoli Liu, Weiwei Lai, Yating Liu, Xiang Wang, Desheng Xiao, Hu Zhou, Yan Cheng, Fenglei Yu, Ya Cao, Shuang Liu, Qin Yan, Yongguang Tao
Ferroptosis is a newly discovered form of non-apoptotic cell death in multiple human diseases. However, the epigenetic mechanisms underlying ferroptosis remain poorly defined. First, we demonstrated that lymphoid-specific helicase (LSH), which is a DNA methylation modifier, interacted with WDR76 to inhibit ferroptosis by activating lipid metabolism-associated genes, including GLUT1, and ferroptosis related genes SCD1 and FADS2, in turn, involved in the Warburg effect. WDR76 targeted these genes expression in dependent manner of LSH and chromatin modification in DNA methylation and histone modification...
2017: Theranostics
https://www.readbyqxmd.com/read/28894242/complementary-acsl-isoforms-contribute-to-a-non-warburg-advantageous-energetic-status-characterizing-invasive-colon-cancer-cells
#8
Ruth Sánchez-Martínez, Silvia Cruz-Gil, María Soledad García-Álvarez, Guillermo Reglero, Ana Ramírez de Molina
Metabolic reprogramming is one of cancer hallmarks. Here, we focus on functional differences and individual contribution of acyl coA synthetases (ACSL) isoforms to the previously described ACSL/stearoyl-CoA desaturase (ACSL1/ACSL4/SCD) metabolic network causing invasion and poor prognosis in colorectal cancer (CRC). ACSL4 fuels proliferation and migration accompanied by a more glycolytic phenotype. Conversely, ACSL1 stimulates invasion displaying a lower basal respiratory rate. Acylcarnitines elevation, polyunsaturated fatty acids (PUFA) lower levels, and monounsaturated fatty acids (MUFA) upregulation characterize the individual overexpression of ACSL1, ACSL4 and SCD, respectively...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28881704/chaperone-mediated-autophagy-substrate-proteins-in-cancer
#9
REVIEW
Ying Tang, Xiong-Wen Wang, Zhan-Hua Liu, Yun-Ming Sun, Yu-Xin Tang, Dai-Han Zhou
All intracellular proteins undergo continuous synthesis and degradation. Chaperone-mediated autophagy (CMA) is necessary to maintain cellular homeostasis through turnover of cytosolic proteins (substrate proteins). This degradation involves a series of substrate proteins including both cancer promoters and suppressors. Since activating or inhibiting CMA pathway to treat cancer is still debated, targeting to the CMA substrate proteins provides a novel direction. We summarize the cancer-associated substrate proteins which are degraded by CMA...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28868241/targeting-cancer-with-tumor-specific-therapeutic-strategies-metabolic-reprogramming-beyond-the-warburg-effect
#10
COMMENT
Paul Grippo, Ajay V Maker
No abstract text is available yet for this article.
May 2017: Translational Cancer Research
https://www.readbyqxmd.com/read/28857035/two-common-variants-of-human-papillomavirus-type-16-e6-differentially-deregulate-sugar-metabolism-and-hypoxia-signalling-in-permissive-human-keratinocytes
#11
Sean Cuninghame, Robert Jackson, Simon J Lees, Ingeborg Zehbe
Human papillomavirus type 16 (HPV16) is responsible for most cancers attributable to HPV infection and naturally occurring variants of the HPV16 E6 oncoprotein predispose individuals to varying risk for developing cancer. Population studies by us and others have demonstrated that the common Asian-American E6 (AAE6) variant is a higher risk factor for cervical cancer than the E6 of another common variant, the European prototype (EPE6). However, a complete understanding of the molecular processes fundamental to these epidemiological findings is still lacking...
September 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28846107/nuclear-factor-e2-related-factor-2-has-a-differential-impact-on-mct1-and-mct4-lactate-carrier-expression-in-colonic-epithelial-cells-a-condition-favoring-metabolic-symbiosis-between-colorectal-cancer-and-stromal-cells
#12
K Diehl, L-A Dinges, O Helm, N Ammar, D Plundrich, A Arlt, C Röcken, S Sebens, H Schäfer
Malignant tumors, such as colorectal cancer (CRC), are heterogeneous diseases characterized by distinct metabolic phenotypes. These include Warburg- and reverse Warburg phenotypes depending on differential distribution of the lactate carrier proteins monocarboxylate transporter-4 and -1 (MCT4 and MCT1). Here, we elucidated the role of the antioxidant transcription factor nuclear factor E2-related factor-2 (Nrf2) as the key regulator of cellular adaptation to inflammatory/environmental stress in shaping the metabolism toward a reverse Warburg phenotype in malignant and premalignant colonic epithelial cells...
August 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28846077/metabolic-cooperation-between-co-cultured-lung-cancer-cells-and-lung-fibroblasts
#13
Michael I Koukourakis, Dimitra Kalamida, Achilleas G Mitrakas, Maria Liousia, Stamatia Pouliliou, Efthimios Sivridis, Alexandra Giatromanolaki
Cooperation of cancer cells with stromal cells, such as cancer-associated fibroblasts (CAFs), has been revealed as a mechanism sustaining cancer cell survival and growth. In the current study, we focus on the metabolic interactions of MRC5 lung fibroblasts with lung cancer cells (A549 and H1299) using co-culture experiments and studying changes of the metabolic protein expression profile and of their growth and migration abilities. Using western blotting, confocal microscopy and RT-PCR, we observed that in co-cultures MRC5 respond by upregulating pyruvate dehydrogenase (PDH) and the monocarboxylate transporter MCT1...
August 28, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28843632/the-warburg-effect-and-glucose-derived-cancer-theranostics
#14
REVIEW
Rakesh K Tekade, Xiankai Sun
Tumor cells are known for their propensity to proliferate uncontrollably and generate multitudes of metastatic masses at the advanced stages of cancer. During this progression, tumor cells switch their energy source from mitochondrial oxidative phosphorylation to a glucose-dependent glycolytic pathway, despite the availability of oxygen. Consequently, tumor cells increase their metabolic rates as well as glucose uptake to maintain their proliferation. This atypical metabolic phenomenon is known as the Warburg effect, which has been recognized as a hallmark of cancer and serves as a promising target for diagnosis and therapy of cancer...
August 24, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28837697/herpesviruses-shape-tumour-microenvironment-through-exosomal-transfer-of-viral-micrornas
#15
Ohad Yogev, Stephen Henderson, Matthew John Hayes, Sara Sofia Marelli, Yifat Ofir-Birin, Neta Regev-Rudzki, Javier Herrero, Tariq Enver
Metabolic changes within the cell and its niche affect cell fate and are involved in many diseases and disorders including cancer and viral infections. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). KSHV latently infected cells express only a subset of viral genes, mainly located within the latency-associated region, among them 12 microRNAs. Notably, these miRNAs are responsible for inducing the Warburg effect in infected cells. Here we identify a novel mechanism enabling KSHV to manipulate the metabolic nature of the tumour microenvironment...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28827059/enhanced-aerobic-glycolysis-of-nasopharyngeal-carcinoma-cells-by-epstein-barr-virus-latent-membrane-protein-1
#16
Wei-Wen Sung, Peir-Rong Chen, Ming-Hui Liao, Jeng-Woei Lee
Latent membrane protein 1 (LMP1) is a principal viral oncoprotein in Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC), which acts through regulating tumorigenesis and metabolic reprogramming of cancers. In the presence of oxygen, we demonstrated that glucose consumption, lactate production and lactate dehydrogenase (LDH) activity were significantly increased upon LMP1 expression in NPC cells and in a LMP1 variant derived from NPC patients-transformed BALB/c-3T3 cells...
August 4, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28819926/targeting-metabolic-pathways-for-head-and-neck-cancers-therapeutics
#17
Masashi Yamamoto, Hidenori Inohara, Takashi Nakagawa
Cancer cells have distinctive energy metabolism pathways that support their rapid cell division. The preference for anaerobic glycolysis under the normal oxygen condition is known as the Warburg effect and has been observed in head and neck cancers. These metabolic changes are controlled by cancer-related transcription factors, such as tumor suppressor gene and hypoxia inducible factor 1α. In addition, various metabolic enzymes also actively regulate cancer-specific metabolism including the switch between aerobic and anaerobic glycolysis...
August 17, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28807238/unravelling-the-complexity-of-signalling-networks-in-cancer-a-review-of-the-increasing-role-for-computational-modelling
#18
REVIEW
John Garland
Cancer induction is a highly complex process involving hundreds of different inducers but whose eventual outcome is the same. Clearly, it is essential to understand how signalling pathways and networks generated by these inducers interact to regulate cell behaviour and create the cancer phenotype. While enormous strides have been made in identifying key networking profiles, the amount of data generated far exceeds our ability to understand how it all "fits together". The number of potential interactions is astronomically large and requires novel approaches and extreme computation methods to dissect them out...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28797070/methyl-pyruvate-protects-a-normal-lung-fibroblast-cell-line-from-irinotecan-induced-cell-death-potential-use-as-adjunctive-to-chemotherapy
#19
Bernice Monchusi, Monde Ntwasa
The Warburg Effect, characterized by increased rate of glycolysis even under normoxic conditions, is one of the hallmarks of cancer. Relatively lower oxidative phosphorylation (OXPHOS) is also a characteristic feature in cancer cells. We hypothesized that interference with this phenomenon, by introducing exogenous pyruvate, would upset this cancer phenotype and boost the energy requirements of normal cells. We find that methyl pyruvate protects irinotecan-treated normal lung fibroblast cell line (MRC-5) probably by turning off the p53/p21 axis of the apoptotic pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28766915/metabolomics-analysis-reveals-distinct-profiles-of-nonmuscle-invasive-and-muscle-invasive-bladder-cancer
#20
Divya Sahu, Yair Lotan, Bryan Wittmann, Bruce Neri, Donna E Hansel
Urothelial carcinoma is the most common form of bladder cancer, but pathway changes that occur with stage-wise progression have not been well defined. We used a metabolomics approach to identify potential metabolic pathways uniquely altered in normal urothelium, nonmuscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC). We performed global metabolomic profiling using GC-mass spectrometry (MS) and LC-MS platforms to identify metabolite signatures between normal urothelium and high-grade urothelial carcinoma of different stages...
August 1, 2017: Cancer Medicine
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