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Warburg effect cancer

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https://www.readbyqxmd.com/read/29331414/inhibition-of-fasn-and-er%C3%AE-signalling-during-hyperglycaemia-induced-matrix-specific-emt-promotes-breast-cancer-cell-invasion-via-a-caveolin-1-dependent-mechanism
#1
H A Zielinska, J M P Holly, A Bahl, C M Perks
Since disturbed metabolic conditions such as obesity and diabetes can be critical determinants of breast cancer progression and therapeutic failure, we aimed to determine the mechanism responsible for their pro-oncogenic effects. Using non-invasive, epithelial-like ERα-positive MCF-7 and T47D human breast cancer cells we found that hyperglycaemia induced epithelial to mesenchymal transition (EMT), a key programme responsible for the development of metastatic disease. This was demonstrated by loss of the epithelial marker E-cadherin together with increases in mesenchymal markers such as vimentin, fibronectin and the transcription factor SLUG, together with an enhancement of cell growth and invasion...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29317493/characterization-of-the-interactions-of-potent-allosteric-inhibitors-with-glutaminase-c-a-key-enzyme-in-cancer-cell-glutamine-metabolism
#2
Qingqiu Huang, Clint Stalnecker, Chengliang Zhang, Lee A McDermott, Prema Iyer, Jason O'Neill, Shawn Reimer, Richard A Cerione, William P Katt
Altered glycolytic flux in cancer cells (the Warburg effect) causes their proliferation to rely upon elevated glutamine metabolism (glutamine addiction). This requirement is met by the overexpression of glutaminase C (GAC), which catalyzes the first step in glutamine metabolism and therefore represents a potential therapeutic target. The small molecule CB-839 was reported to be more potent than other allosteric GAC inhibitors, including the parent compound BPTES, and is in clinical trials. Recently, we described the synthesis of BPTES analogs having distinct saturated heterocyclic cores as a replacement for the flexible chain moiety, with improved microsomal stability relative to CB-839 and BPTES...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29306548/disrupting-the-warburg-effect-re-routes-cancer-cells-to-oxphos-offering-a-vulnerability-point-via-ferroptosis-induced-cell-death
#3
REVIEW
Maša Ždralević, Milica Vučetić, Boutaina Daher, Ibtissam Marchiq, Scott K Parks, Jacques Pouysségur
The evolution of life from extreme hypoxic environments to an oxygen-rich atmosphere has progressively selected for successful metabolic, enzymatic and bioenergetic networks through which a myriad of organisms survive the most extreme environmental conditions. From the two lethal environments anoxia/high O2, cells have developed survival strategies through expression of the transcriptional factors ATF4, HIF1 and NRF2. Cancer cells largely exploit these factors to thrive and resist therapies. In this review, we report and discuss the potential therapeutic benefit of disrupting the major Myc/Hypoxia-induced metabolic pathway, also known as fermentative glycolysis or "Warburg effect", in aggressive cancer cell lines...
December 28, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29296215/cell-surface-grp78-promotes-tumor-cell-histone-acetylation-through-metabolic-reprogramming-a-mechanism-which-modulates-the-warburg-effect
#4
Udhayakumar Gopal, Salvatore V Pizzo
Acetyl coenzyme A (acetyl-CoA) is essential for histone acetylation, to promote cell proliferation by regulating gene expression. However, the underlying mechanism(s) governing acetylation remains poorly understood. Activated α2-Macroglobulin (α2M*) signals through tumor Cell Surface GRP78 (CS-GRP78) to regulate tumor cell proliferation through multiple signaling pathway. Here, we demonstrate that the α2M*/CS-GRP78 axis regulates acetyl-CoA synthesis and thus functions as an epigenetic modulator by enhancing histone acetylation in cancer cells...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290953/viral-e6-e7-oncogene-and-cellular-hexokinase-2-expression-in-hpv-positive-cancer-cell-lines
#5
Karin Hoppe-Seyler, Anja Honegger, Felicitas Bossler, Jasmin Sponagel, Julia Bulkescher, Claudia Lohrey, Felix Hoppe-Seyler
Oncogenic types of human papillomaviruses (HPVs) are major human carcinogens. Cancer cells typically exhibit metabolic alterations which support their malignant growth. These include an enhanced rate of aerobic glycolysis ('Warburg effect') which in cancer cells is often linked to an increased expression of the rate-limiting glycolytic enzyme Hexokinase 2 (HK2). Intriguingly, recent studies indicate that the HPV E6/E7 oncogenes cause the metabolic reprogramming in HPV-positive cancer cells by directly upregulating HK2 expression...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290768/modulated-electro-hyperthermia-induced-loco-regional-and-systemic-tumor-destruction-in-colorectal-cancer-allografts
#6
Tamas Vancsik, Csaba Kovago, Eva Kiss, Edina Papp, Gertrud Forika, Zoltan Benyo, Nora Meggyeshazi, Tibor Krenacs
Background: Modulated electro-hyperthermia (mEHT), a non-invasive intervention using 13.56 MHz radiofrequency, can selectively target cancers due to their elevated glycolysis (Warburg-effect), extracellular ion concentration and conductivity compared to normal tissues. We showed earlier that mEHT alone can provoke apoptosis and damage associated molecular pattern (DAMP) signals in human HT29 colorectal cancer xenografts of immunocompromised mice. Materials: Here we tested the mEHT induced stress and immune responses in C26 colorectal cancer allografts of immunocompetent (BALB/c) mice between 12-72 h post-treatment...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29289511/opening-of-voltage-dependent-anion-channels-promotes-reactive-oxygen-species-generation-mitochondrial-dysfunction-and-cell-death-in-cancer-cells
#7
David N DeHart, Diana Fang, Kareem Heslop, Li Li, John J Lemasters, Eduardo N Maldonado
Enhancement of aerobic glycolysis and suppression of mitochondrial metabolism characterize the pro-proliferative Warburg phenotype of cancer cells. High free tubulin in cancer cells closes voltage dependent anion channels (VDAC) to decrease mitochondrial membrane potential (ΔΨ), an effect antagonized by erastin, the canonical promotor of ferroptosis. Previously, we identified six compounds (X1-X6) that also block tubulin-dependent mitochondrial depolarization. Here, we hypothesized that VDAC opening after erastin and X1-X6 increases mitochondrial metabolism and reactive oxygen species (ROS) formation, leading to ROS-dependent mitochondrial dysfunction, bioenergetic failure and cell death...
December 28, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29282687/metabolic-changes-during-cancer-cachexia-pathogenesis
#8
Ng Shyh-Chang
Wasting of adipose tissue and skeletal muscle is a hallmark of metastatic cancer and a major cause of death. Like patients with cachexia caused by other chronic infections or inflammatory diseases, the cancer subject manifests both malnutrition and metabolic stress. Both carbohydrate utilization and amino acid incorporation are decreased in the muscles of cancer cachexia patients. Cancer cells affect host metabolism in two ways: (a) their own metabolism of nutrients into other metabolites and (b) circulating factors they secrete or induce the host to secrete...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29279329/purine-nucleotide-metabolism-regulates-expression-of-the-human-immune-ligand-mica
#9
Michael T McCarthy, Gerald Moncayo, Thomas K Hiron, Niels A Jakobsen, Alessandro Vali, Tomoyoshi Soga, Julie Adam, Christopher A O'Callaghan
Expression of the cell surface glycoprotein MHC class I polypeptide-related sequence A (MICA) is induced in dangerous, abnormal or 'stressed' cells, including cancer cells, virus-infected cells and rapidly proliferating cells. MICA is recognized by the activating immune cell receptor NKG2D, providing a mechanism by which immune cells can identify and potentially eliminate pathological cells. Immune recognition through NKG2D is implicated in cancer, atherosclerosis, transplant rejection and inflammatory diseases such as rheumatoid arthritis...
December 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29250326/palliative-treatment-efficacy-of-glucose-inhibition-combined-with-chemotherapy-for-non-small-cell-lung-cancer-with-widespread-bone-and-brain-metastases-a-case-report
#10
Yongping Liu, Yaping Zhang, Xibao Mao, Qiufeng Qi, Ming Zhu, Changsong Zhang, Xuefeng Pan, Yang Ling
Otto Warburg observed in 1924 that cancer cells were dependent exclusively on glycolysis for the production of energy even in the presence of oxygen (the 'Warburg effect'). Consequently, cancer cells require ~19 times more glucose uptake to obtain equivalent amounts of energy as normal cells. The Warburg effect is the scientific basis for positron emission tomography (PET), which has markedly improved cancer detection. During chemotherapy, cancer cells may upregulate their expression of multi-drug resistance proteins and ultimately cause treatment failure...
December 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29248131/metabolic-coupling-and-the-reverse-warburg-effect-in-cancer-implications-for-novel-biomarker-and-anticancer-agent-development
#11
REVIEW
Lindsay Wilde, Megan Roche, Marina Domingo-Vidal, Katherina Tanson, Nancy Philp, Joseph Curry, Ubaldo Martinez-Outschoorn
Glucose is a key metabolite used by cancer cells to generate ATP, maintain redox state and create biomass. Glucose can be catabolized to lactate in the cytoplasm, which is termed glycolysis, or alternatively can be catabolized to carbon dioxide and water in the mitochondria via oxidative phosphorylation. Metabolic heterogeneity exists in a subset of human tumors, with some cells maintaining a glycolytic phenotype while others predominantly utilize oxidative phosphorylation. Cells within tumors interact metabolically with transfer of catabolites from supporting stromal cells to adjacent cancer cells...
June 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/29229835/o-glcnacylation-destabilizes-the-active-tetrameric-pkm2-to-promote-the-warburg-effect
#12
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
#13
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
#14
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 8, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29221144/ucp2-overexpression-enhanced-glycolysis-via-activation-of-pfkfb2-during-skin-cell-transformation
#15
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
#16
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
#17
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
#18
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...
January 1, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29212301/convergence-of-cancer-metabolism-and-immunity-an-overview
#19
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...
January 1, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29207896/rho-gtpase-effectors-and-nad-metabolism-in-cancer-immune-suppression
#20
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
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