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Warburg effect cancer

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https://www.readbyqxmd.com/read/28541512/the-interplay-between-metabolic-remodeling-and-immune-regulation-in-glioblastoma
#1
Pravin Kesarwani, Shiva Kant, Antony Prabhu, Prakash Chinnaiyan
The fields of tumor metabolism and immune oncology have both independently received considerable attention over the last several years. The majority of research in tumor metabolism has largely focused on the Warburg effect and its resulting biologic consequences, including energy and macromolecule production. However, recent investigations have identified elegant, multifaceted strategies by which alterations in tumor metabolism can also contribute towards a potent tolerogenic immune environment. One of the most notable is increased tryptophan metabolism through activation of the indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) pathways...
May 25, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28539549/the-metabolic-regulation-in-immune-cells-and-pathogenesis-of-systemic-lupus-erythematosus-%C3%A2-toward-new-therapeutic-applications%C3%A2
#2
Yusuke Takeshima, Yukiko Iwasaki, Tomohisa Okamura, Keishi Fujio, Kazuhiko Yamamoto
  The importance of cellular metabolism has long been known as Warburg effect; cancer cells are characterized by mitochondrial defect that shifts towards aerobic glycolysis. Recently, many reports have revealed that immune metabolism is a key factor for controlling immune cell proliferation and differentiation. Resting lymphocytes generate energy through oxidative phosphorylation and fatty acid oxidation, whereas activated lymphocytes rapidly shift to glycolysis. Especially in T cells, more precise mechanism of regulating metabolism have been clarified on differentiation from naïve T cells to effector T cells...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28532652/inhibition-of-glycolysis-by-a-novel-egfr-her2-inhibitor-ku004-suppresses-the-growth-of-her2-cancer
#3
Chongchong Tian, Ziqiao Yuan, Dengqiu Xu, Pingping Ding, Tao Wang, Luyong Zhang, Zhenzhou Jiang
Upregulation of glycolysis was often observed in human HER2-overexpressing cancers. In this study, we demonstrated that KU004, a dual novel EGFR/HER2 inhibitor, disrupted cancer cell proliferation via modulation of glycolysis. KU004, inhibited the Warburg effect by suppressing hexokinase II (HK2) expression at the transcptional and post-translational levels. Further study demonstrated that the downregulation of HKII by KU004 was mainly mediated by the PI3K/Akt signaling pathway. Furthermore, the role of HKII downregulation in KU004-mediated antitumor effect was also confirmed in our in vivo xenograft model...
May 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28529605/mutual-regulation-of-mir-199a-5p-and-hif-1%C3%AE-modulates-the-warburg-effect-in-hepatocellular-carcinoma
#4
Binkui Li, Liru He, Dinglan Zuo, Wei He, Yongjin Wang, Yuanping Zhang, Wenwu Liu, Yunfei Yuan
The Warburg effect is one of the major metabolic changes of cancer cells, which characterized by high level of glycolysis even in the presence of oxygen. However, the role of microRNAs (miRNAs) in regulating the glycolytic switch in cancer cells has not been well explored. In this study, we demonstrated that miR-199a-5p acts as a suppressor of the Warburg effect in hepatocellular carcinoma (HCC). MiR-199a-5p directly targets the 3'-untranslated region (UTR) of hypoxia-inducible factor-1α (HIF-1α), thereby suppressing glucose uptake, lactate production, cell growth, and expression of HIF-1α downstream glycolytic genes of HCC cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28516914/adenylate-kinase-hcinap-determines-self-renewal-of-colorectal-cancer-stem-cells-by-facilitating-ldha-phosphorylation
#5
Yapeng Ji, Chuanzhen Yang, Zefang Tang, Yongfeng Yang, Yonglu Tian, Hongwei Yao, Xi Zhu, Zeming Zhang, Jiafu Ji, Xiaofeng Zheng
Targeting the specific metabolic phenotypes of colorectal cancer stem cells (CRCSCs) is an innovative therapeutic strategy for colorectal cancer (CRC) patients with poor prognosis and relapse. However, the context-dependent metabolic traits of CRCSCs remain poorly elucidated. Here we report that adenylate kinase hCINAP is overexpressed in CRC tissues. Depletion of hCINAP inhibits invasion, self-renewal, tumorigenesis and chemoresistance of CRCSCs with a loss of mesenchymal signature. Mechanistically, hCINAP binds to the C-terminal domain of LDHA, the key regulator of glycolysis, and depends on its adenylate kinase activity to promote LDHA phosphorylation at tyrosine 10, resulting in the hyperactive Warburg effect and the lower cellular ROS level and conferring metabolic advantage to CRCSC invasion...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28515353/chaperone-mediated-autophagy-substrate-proteins-in-cancer
#6
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...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512002/cell-surface-g-protein-coupled-receptors-for-tumor-associated-metabolites-a-direct-link-to-mitochondrial-dysfunction-in-cancer
#7
REVIEW
Bojana Ristic, Yangzom D Bhutia, Vadivel Ganapathy
Mitochondria are the sites of pyruvate oxidation, citric acid cycle, oxidative phosphorylation, ketogenesis, and fatty acid oxidation. Attenuation of mitochondrial function is one of the most significant changes that occurs in tumor cells, directly linked to oncogenesis, angiogenesis, Warburg effect, and epigenetics. In particular, three mitochondrial enzymes are inactivated in cancer: pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and 3-hydroxy-3-methylglutaryl CoA synthase-2 (HMGCS2). These enzymes are subject to regulation via acetylation/deacetylation...
May 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28508297/adaptation-to-stochastic-temporal-variations-in-intratumoral-blood-flow-the-warburg-effect-as-a-bet-hedging-strategy
#8
Curtis A Gravenmier, Miriam Siddique, Robert A Gatenby
While most cancers promote ingrowth of host blood vessels, the resulting vascular network usually fails to develop a mature organization, resulting in abnormal vascular dynamics with stochastic variations that include slowing, cessation, and even reversal of flow. Thus, substantial spatial and temporal variations in oxygen concentration are commonly observed in most cancers. Cancer cells, like all living systems, are subject to Darwinian dynamics such that their survival and proliferation are dependent on developing optimal phenotypic adaptations to local environmental conditions...
May 15, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28501492/ldh-inhibition-impacts-on-heat-shock-response-and-induces-senescence-of-hepatocellular-carcinoma-cells
#9
Marcella Manerba, Lorenza Di Ianni, Marzia Govoni, Marinella Roberti, Maurizio Recanatini, Giuseppina Di Stefano
In normal cells, heat shock response (HSR) is rapidly induced in response to a variety of harmful conditions and represents one of the most efficient defense mechanism. In cancer tissues, constitutive activation converts HSR into a life-threatening process, which plays a major role in helping cell survival and proliferation. Overexpression of heat shock proteins (HSPs) has been widely reported in human cancers and was found to correlate with tumor progression. Hepatocellular carcinoma is one of the conditions in which HSR activation was shown to have the highest clinical significance...
May 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28499577/metabolic-regulation-of-suppressive-myeloid-cells-in-cancer
#10
REVIEW
Antonio Sica, Laura Strauss, Francesca Maria Consonni, Cristina Travelli, Armando Genazzani, Chiara Porta
Cancer cells rewire their metabolism to promote growth, survival, proliferation and long-term maintenance. The common feature of this altered metabolism is the increased glucose uptake and fermentation of glucose to lactate, which is observed even in the presence of completely functioning mitochondria. This effect is known as the 'Warburg Effect' and its intensive investigation in the last decade has partially established either its causes or its functions. It is now emerging that a major side effect of the Warburg Effect is immunosuppression, which limits the immunogenicity of cancer cells and therefore restricts the therapeutic efficacy of anticancer immunotherapy...
May 3, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28491867/metabolic-reprogramming-in-glioma
#11
REVIEW
Marie Strickland, Elizabeth A Stoll
Many cancers have long been thought to primarily metabolize glucose for energy production-a phenomenon known as the Warburg Effect, after the classic studies of Otto Warburg in the early twentieth century. Yet cancer cells also utilize other substrates, such as amino acids and fatty acids, to produce raw materials for cellular maintenance and energetic currency to accomplish cellular tasks. The contribution of these substrates is increasingly appreciated in the context of glioma, the most common form of malignant brain tumor...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28488732/involvement-of-the-warburg-effect-in-non-tumor-diseases-processes
#12
REVIEW
Zhe Chen, Meiqing Liu, Lanfang Li, Linxi Chen
Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg effect plays a crucial role in non-tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension. Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure...
May 10, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28482870/effect-of-the-cancer-specific-shorter-form-of-human-6-phosphofructo-1-kinase-on-the-metabolism-of-the-yeast-saccharomyces-cerevisiae
#13
Darjan Andrejc, Alenka Možir, Matic Legiša
BACKGROUND: At first glance, there appears to be a high degree of similarity between the metabolism of yeast (the Crabtree effect) and human cancer cells (the Warburg effect). At the root of both effects is accelerated metabolic flow through glycolysis which leads to overflows of ethanol and lactic acid, respectively. It has been proposed that enhanced glycolytic flow in cancer cells is triggered by the altered kinetic characteristics of the key glycolytic regulatory enzyme 6-phosphofructo-1-kinase (Pfk)...
May 8, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28471448/mir-1-suppresses-tumor-cell-proliferation-in-colorectal-cancer-by-inhibition-of-smad3-mediated-tumor-glycolysis
#14
Wanfu Xu, Zijing Zhang, Kejian Zou, Yang Cheng, Min Yang, Huan Chen, Hongli Wang, Junhong Zhao, Peiyu Chen, Liying He, Xinwen Chen, Lanlan Geng, Sitang Gong
Aberrant expression of microRNA (miR)-1 has been observed in many human malignancies. However, the function and underlying mechanism of miR-1 remains elusive. To address the specific role of miR-1 in tumor glycolysis using the gain- or loss-of-function studies. Metabolic studies combined with gene expression analysis were performed in vitro and in vivo. We demonstrated aberrant expression of miR-1 in aerobic glycolysis, the Warburg effect, in cancer cells. MiR-1 suppressed aerobic glycolysis and tumor cell proliferation via inactivation of Smad3 and targeting HIF-1α, leading to reduce HK2 and MCT4 expression, which illustrated a novel pathway to mediate aerobic glycolysis in cancer cells...
May 4, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28467806/glut1-mediated-selective-tumor-targeting-with-fluorine-containing-platinum-ii-glycoconjugates
#15
Ran Liu, Zheng Fu, Meng Zhao, Xiangqian Gao, Hong Li, Qian Mi, Pengxing Liu, Jinna Yang, Zhi Yao, Qingzhi Gao
Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glucose, mannose and galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-flouromalonato-platinum(II) complexes for a comprehensive evaluation on their selective tumor targeting...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28467784/in-silico-gene-expression-analysis-reveals-glycolysis-and-acetate-anaplerosis-in-idh1-wild-type-glioma-and-lactate-and-glutamate-anaplerosis-in-idh1-mutated-glioma
#16
Mohammed Khurshed, Remco J Molenaar, Krissie Lenting, William P Leenders, Cornelis J F van Noorden
Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) initiate low-grade glioma and secondary glioblastoma and induce a neomorphic activity that converts α-ketoglutarate (α-KG) to the oncometabolite D-2-hydroxyglutarate (D-2-HG). It causes metabolic rewiring that is not fully understood. We investigated the effects of IDH1 mutations (IDH1MUT) on expression of genes that encode for metabolic enzymes by data mining The Cancer Genome Atlas. We analyzed 112 IDH1 wild-type (IDH1WT) versus 399 IDH1MUT low-grade glioma and 157 IDH1WT versus 9 IDH1MUT glioblastoma samples...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28461244/mir-30a-5p-suppresses-breast-tumor-growth-and-metastasis-through-inhibition-of-ldha-mediated-warburg-effect
#17
Ling Li, Lei Kang, Wei Zhao, Yingying Feng, Wenpeng Liu, Tao Wang, Haixing Mai, Jun Huang, Siyu Chen, Yingchun Liang, Juqiang Han, Xiaojie Xu, Qinong Ye
Lactate dehydrogenase A (LDHA), a key enzyme regulating aerobic glycolysis, is overexpressed in many human cancers, and correlates with poor clinical outcomes. Aerobic glycolysis is a hallmark of cancer, and drugs targeting its regulators, including LDHA, are being developed. However, the mechanisms of LDHA inhibition and the physiological significance of the LDHA inhibitors in cancer cells are unclear. Here, we show that microRNA-30a-5p (miR-30a-5p) suppresses LDHA expression by directly targeting its 3'-UTR...
April 29, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28453233/proteomic-analysis-of-oral-cancer-reveals-new-potential-therapeutic-targets-involved-in-the-warburg-effect
#18
Yi-Ping Huang, Nai Wen Chang
Activation of peroxisome proliferator-activated receptor alpha (PPARα) has been reported to disrupt tumor metabolism and to promote anticancer activity through interfering with the Warburg effect. This study is to investigate whether Warburg effect-related proteins also could be identified in the oral tumor lesions and to explore the functional significance of PPARα in metabolic shift. Five pairs of tongue tumor tissues and adjacent reference tissues obtained from 4-NQO/arecoline induced mouse model were analyzed by 2-D-gel-electrophoresis and LC-MS...
April 28, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28448945/teaching-the-basics-of-cancer-metabolism-developing-antitumor-strategies-by-exploiting-the-differences-between-normal-and-cancer-cell-metabolism
#19
REVIEW
Balaraman Kalyanaraman
This review of the basics of cancer metabolism focuses on exploiting the metabolic differences between normal and cancer cells. The first part of the review covers the different metabolic pathways utilized in normal cells to generate cellular energy, or ATP, and the glycolytic intermediates required to build the cellular machinery. The second part of the review discusses aerobic glycolysis, or the Warburg effect, and the metabolic reprogramming involving glycolysis, tricarboxylic acid cycle, and glutaminolysis in the context of developing targeted inhibitors in cancer cells...
April 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28442214/regulatory-t-cells-as-suppressors-of-anti-tumor-immunity-role-of-metabolism
#20
REVIEW
Veronica De Rosa, Francesca Di Rella, Antonio Di Giacomo, Giuseppe Matarese
Novel concepts in immunometabolism support the hypothesis that glucose consumption is also used to modulate anti-tumor immune responses, favoring growth and expansion of specific cellular subsets defined in the past as suppressor T cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto Warburg and colleagues observed that tumors consumed high amounts of glucose compared to normal tissues, even in the presence of oxygen and completely functioning mitochondria. However, the role of the Warburg Effect is still not completely understood, particularly in the context of an ongoing anti-tumor immune response...
April 11, 2017: Cytokine & Growth Factor Reviews
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