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https://www.readbyqxmd.com/read/28624784/mitochondrial-pyruvate-carrier-function-determines-cell-stemness-and-metabolic-reprogramming-in-cancer-cells
#1
Xiaoli Li, Gaoyang Han, Xiaoran Li, Quancheng Kan, Zhirui Fan, Yaqing Li, Yasai Ji, Jing Zhao, Mingzhi Zhang, Mantas Grigalavicius, Viktor Berge, Mariusz Adam Goscinski, Jahn M Nesland, Zhenhe Suo
One of the remarkable features of cancer cells is aerobic glycolysis, a phenomenon known as the "Warburg Effect", in which cells rely preferentially on glycolysis instead of oxidative phosphorylation (OXPHOS) as the main energy source even in the presence of high oxygen tension. Cells with dysfunctional mitochondria are unable to generate sufficient ATP from mitochondrial OXPHOS, and then are forced to rely on glycolysis for ATP generation. Here we report our results in a prostate cancer cell line in which the mitochondrial pyruvate carrier 1 (MPC1) gene was knockout...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622688/integration-of-metabolomics-transcriptomics-and-microrna-expression-profiling-reveals-a-mir-143-hk2-glucose-network-underlying-zinc-deficiency-associated-esophageal-neoplasia
#2
Louise Y Fong, Ruiyan Jing, Karl J Smalley, Cristian Taccioli, Johannes Fahrmann, Dinesh K Barupal, Hansjuerg Alder, John L Farber, Oliver Fiehn, Carlo M Croce
Esophageal squamous cell carcinoma (ESCC) in humans is a deadly disease associated with dietary zinc (Zn)-deficiency. In the rat esophagus, Zn-deficiency induces cell proliferation, alters mRNA and microRNA gene expression, and promotes ESCC. We investigated whether Zn-deficiency alters cell metabolism by evaluating metabolomic profiles of esophageal epithelia from Zn-deficient and replenished rats vs sufficient rats, using untargeted gas chromatography time-of-flight mass spectrometry (n = 8/group). The Zn-deficient proliferative esophagus exhibits a distinct metabolic profile with glucose down 153-fold and lactic acid up 1...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620312/thermodynamics-in-gliomas-interactions-between-the-canonical-wnt-beta-catenin-pathway-and-ppar-gamma
#3
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Gliomas cells are the site of numerous metabolic and thermodynamics abnormalities with an increasing entropy rate which is characteristic of irreversible processes driven by changes in Gibbs energy, heat production, intracellular acidity, membrane potential gradient, and ionic conductance. We focus our review on the opposing interactions observed in glioma between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In gliomas, WNT/beta-catenin pathway is upregulated while PPAR gamma is downregulated...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28618597/role-of-the-displacement-current-on-warburg-type-behavior
#4
I Lelidis, G Barbero
We investigate the role of the displacement current in the analysis of the electric response of an electrolytic cell to an external stimulus. We show that several models proposed to interpret the spectra deduced by means of the impedance spectroscopy technique are questionable. In particular, we demonstrate that even in the frequency range below the Debye frequency the role of the displacement current is fundamental, and its omission leads to incorrect results for the impedance of the cell. In our analysis, the boundary conditions on the bulk current density are of Nernstian and of Ohmic type...
May 2017: Physical Review. E
https://www.readbyqxmd.com/read/28617852/dicumarol-inhibits-pdk1-and-targets-multiple-malignant-behaviors-of-ovarian-cancer-cells
#5
Wenjia Zhang, Jing Su, Huadan Xu, Shanshan Yu, Yanan Liu, Yong Zhang, Liankun Sun, Ying Yue, Xiaoli Zhou
Pyruvate dehydrogenase kinase 1 (PDK1) is overexpressed in ovarian cancer and thus is a promising anticancer therapeutic target. Our previous work suggests that coumarin compounds are potential inhibitors of PDKs. In this study, we used the ovarian cancer cell line SKOV3 as the model system and examined whether dicumarol (DIC), a coumarin compound, could inhibit ovarian cancer through targeting PDK1. We showed that DIC potently inhibited the kinase activity of PDK1, shifted the glucose metabolism from aerobic glycolysis to oxidative phosphorylation, generated a higher level of reactive oxygen species (ROS), attenuated the mitochondrial membrane potential (MMP), induced apoptosis, and reduced cell viability in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28616574/therapeutic-arginine-starvation-in-ass1-deficient-cancers-inhibits-the-warburg-effect
#6
Jeff C Kremer, Brian A Van Tine
Argininosuccinate Synthetase 1 deficiency induces dependence on extracellular arginine for continued cellular growth and survival. Arginine starvation inhibits the Warburg effect and diverts glucose into serine biosynthesis, while simultaneously increasing glutamine metabolism via the tricarboxylic acid cycle. Simultaneous arginine deprivation and inhibition of the subsequent metabolic adaptations induce synthetic lethality.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28616398/new-photodynamic-therapy-with-next-generation-photosensitizers
#7
REVIEW
Hiromi Kataoka, Hirotada Nishie, Noriyuki Hayashi, Mamoru Tanaka, Akihiro Nomoto, Shigenobu Yano, Takashi Joh
Photodynamic therapy (PDT) is a non-invasive antitumor treatment that uses the combination of a photosensitizer, tissue oxygen, and visible light irradiation to produce cytotoxic reactive oxygen species, predominantly singlet oxygen. Currently, first-generation PDT using porfimer sodium with an excimer dye laser, and second-generation PDT using talaporfin sodium PDT with a semiconductor laser are approved by health insurance for use in Japan. However, the cancer cell specificity and selectivity of these treatments are inadequate...
April 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28615519/the-reverse-warburg-effect-is-likely-to-be-an-achilles-heel-of-cancer-that-can-be-exploited-for-cancer-therapy
#8
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...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611773/fatty-acid-oxidation-compensates-for-lipopolysaccharide-induced-warburg-effect-in-glucose-deprived-monocytes
#9
Nora Raulien, Kathleen Friedrich, Sarah Strobel, Stefan Rubner, Sven Baumann, Martin von Bergen, Antje Körner, Martin Krueger, Manuela Rossol, Ulf Wagner
Monocytes enter sites of microbial or sterile inflammation as the first line of defense of the immune system and initiate pro-inflammatory effector mechanisms. We show that activation with bacterial lipopolysaccharide (LPS) induces them to undergo a metabolic shift toward aerobic glycolysis, similar to the Warburg effect observed in cancer cells. At sites of inflammation, however, glucose concentrations are often drastically decreased, which prompted us to study monocyte function under conditions of glucose deprivation and abrogated Warburg effect...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28603693/cancer-untethering-mitochondria-from-the-endoplasmic-reticulum
#10
REVIEW
Maria Sol Herrera-Cruz, Thomas Simmen
Following the discovery of the mitochondria-associated membrane (MAM) as a hub for lipid metabolism in 1990 and its description as one of the first examples for membrane contact sites at the turn of the century, the past decade has seen the emergence of this structure as a potential regulator of cancer growth and metabolism. The mechanistic basis for this hypothesis is that the MAM accommodates flux of Ca(2+) from the endoplasmic reticulum (ER) to mitochondria. This flux then determines mitochondrial ATP production, known to be low in many tumors as part of the Warburg effect...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28602700/long-non-coding-rna-pvt1-promotes-glycolysis-and-tumor-progression-by-regulating-mir-497-hk2-axis-in-osteosarcoma
#11
Jingyi Song, Xiaolin Wu, Fengxia Liu, Maohua Li, Yuerong Sun, Yan Wang, Chao Wang, Kai Zhu, Xiujuan Jia, Bing Wang, Xuexiao Ma
Cancer cells usually utilize glucose as a carbon source for aerobic glycolysis, a phenomenon known as the Warburg effect. Increasing studies have shown that PVT1 (a long non-coding RNA, lncRNA) functions as critical regulator of multiple cancers. However, it remains totally unknown whether and how PVT1 regulates glucose metabolism in OS cells. In this study, we found that the expression of PVT1 were specifically increased in OS cells and tissues, and the upregulated PVT1 indicated poor prognosis. Glucose uptake, lactate production, and the expression of HK2 in OS cells were increased by overexpression of PVT1, while decreased by PVT1 knockdown...
June 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28597070/the-kiss1-metastasis-suppressor-appears-to-reverse-the-warburg-effect-by-shifting-from-glycolysis-to-mitochondrial-beta-oxidation
#12
Sharon J Manley, Wen Liu, Danny R Welch
The shift by cancer cells toward aerobic glycolysis (Warburg effect) confers selective advantages by utilizing nutrients (e.g., lipids, amino acids, and nucleotides) to build biomass. Lipogenesis is generally enhanced, and its inhibition diminishes proliferation and survival. Re-expression of the metastasis suppressor KISS1 in human melanoma cells results in greater mitochondrial biogenesis, inhibition of glycolysis, utilization of beta-oxidation to provide energy, elevated oxidation of exogenous fatty acids, and increased expression of early-phase lipogenesis genes at both mRNA and protein levels...
June 8, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28596605/microenvironmental-cooperation-promotes-early-spread-and-bistability-of-a-warburg-like-phenotype
#13
Jorge Fernandez-de-Cossio-Diaz, Andrea De Martino, Roberto Mulet
We introduce an in silico model for the initial spread of an aberrant phenotype with Warburg-like overflow metabolism within a healthy homeostatic tissue in contact with a nutrient reservoir (the blood), aimed at characterizing the role of the microenvironment for aberrant growth. Accounting for cellular metabolic activity, competition for nutrients, spatial diffusion and their feedbacks on aberrant replication and death rates, we obtain a phase portrait where distinct asymptotic whole-tissue states are found upon varying the tissue-blood turnover rate and the level of blood-borne primary nutrient...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28596599/the-mir-125a-hk2-axis-regulates-cancer-cell-energy-metabolism-reprogramming-in-hepatocellular-carcinoma
#14
Fangfang Jin, Yanbo Wang, Yanan Zhu, Shan Li, Ying Liu, Cheng Chen, Xiaohua Wang, Ke Zen, Limin Li
The Warburg effect is a metabolic hallmark of cancer. Tumor cells rapidly adjust their energy source to glycolysis in order to efficiently proliferate in a hypoxic environment, but the mechanism underlying this switch remains incompletely understood. Here, we show that hypoxia potently induces the down-regulation of miR-125a expression in hepatocellular carcinoma (HCC) cells and tumors. Furthermore, we demonstrate that miR-125a could decrease the production of lactate, the uptake of glucose, and the levels of ATP and reactive oxygen species (ROS) in HCC cells...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28591165/dichloroacetate-affects-proliferation-but-not-apoptosis-in-canine-mammary-cell-lines
#15
Tatjana P Harting, Mandy Stubbendorff, Susanne C Hammer, Patrik Schadzek, Anaclet Ngezahayo, Hugo Murua Escobar, Ingo Nolte
Targeting mitochondrial energy metabolism is a novel approach in cancer research and can be traced back to the description of the Warburg effect. Dichloroacetate, a controversially discussed subject of many studies in cancer research, is a pyruvate dehydrogenase kinase inhibitor. Dichloroacetate causes metabolic changes in cancerous glycolysis towards oxidative phosphorylation via indirect activation of pyruvate dehydrogenase in mitochondria. Canine mammary cancer is frequently diagnosed but after therapy prognosis still remains poor...
2017: PloS One
https://www.readbyqxmd.com/read/28580187/associations-among-metabolism-circadian-rhythm-and-age-associated-diseases
#16
REVIEW
Yiwei Cao, Rui-Hong Wang
Accumulating epidemiological studies have implicated a strong link between age associated metabolic diseases and cancer, though direct and irrefutable evidence is missing. In this review, we discuss the connection between Warburg effects and tumorigenesis, as well as adaptive responses to environment such as circadian rhythms on molecular pathways involved in metabolism. We also review the central role of the sirtuin family of proteins in physiological modulation of cellular processes and age-associated metabolic diseases...
May 2017: Aging and Disease
https://www.readbyqxmd.com/read/28579513/micrornas-and-altered-metabolism-of-clear-cell-renal-cell-carcinoma-potential-role-as-aerobic-glycolysis-biomarkers
#17
REVIEW
Mariana Morais, Francisca Dias, Ana L Teixeira, Rui Medeiros
BACKGROUND: Warburg Effect is a metabolic switch that occurs in most of cancer cells but its advantages are not fully understood. This switch is known to happen in renal cell carcinoma (RCC), which is the most common solid cancer of the adult kidney. RCC carcinogenesis is related to pVHL loss and Hypoxia Inducible Factor (HIF) activation, ultimately leading to the activation of several genes related to glycolysis. MicroRNAs (miRNAs) regulate gene expression at a post-transcriptional level and are also deregulated in several cancers, including RCC...
June 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28574758/warburg-effect-damping-of-electromagnetic-oscillations
#18
Jiří Pokorný, Jan Pokorný, Fedir Borodavka
Mitochondrial dysfunction is a central defect in cells creating the Warburg and reverse Warburg effect cancers. However, the link between mitochondrial dysfunction and cancer has not yet been clearly explained. Decrease of mitochondrial oxidative energy production to about 50 % in comparison with healthy cells may be caused by inhibition of pyruvate transfer into mitochondrial matrix and/or disturbed H(+) ion transfer across inner mitochondrial membrane into cytosol. Lowering of the inner membrane potential and shifting of the working point of mitochondria to high values of pH above an intermediate point causes reorganization of the ordered water layer at the mitochondrial membrane...
June 2, 2017: Electromagnetic Biology and Medicine
https://www.readbyqxmd.com/read/28561705/metabolic-alterations-in-cancer-and-their-potential-as-therapeutic-targets
#19
Jamie D Weyandt, Craig B Thompson, Amato J Giaccia, W Kimryn Rathmell
Otto Warburg's discovery in the 1920s that tumor cells took up more glucose and produced more lactate than normal cells provided the first clues that cancer cells reprogrammed their metabolism. For many years, however, it was unclear as to whether these metabolic alterations were a consequence of tumor growth or an adaptation that provided a survival advantage to these cells. In more recent years, interest in the metabolic differences in cancer cells has surged, as tumor proliferation and survival have been shown to be dependent upon these metabolic changes...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28559292/brucella-abortus-induces-a-warburg-shift-in-host-metabolism-that-is-linked-to-enhanced-intracellular-survival-of-the-pathogen
#20
Daniel M Czyż, Jonathan Willett, Sean Crosson
Intracellular bacterial pathogens exploit host cell resources to replicate and survive inside the host. Targeting these host systems is one promising approach to developing novel antimicrobials to treat intracellular infections. We show that human macrophage-like cells infected with Brucella abortus undergo a metabolic shift characterized by attenuated tricarboxylic acid cycle metabolism, reduced amino acid consumption, altered mitochondrial localization, and increased lactate production. This shift to an aerobic glycolytic state resembles the Warburg effect, a change in energy production that is well-described in cancer cells, and also occurs in activated inflammatory cells...
May 30, 2017: Journal of Bacteriology
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