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https://www.readbyqxmd.com/read/27912843/the-reduced-concentration-of-citrate-in-cancer-cells-an-indicator-of-cancer-aggressiveness-and-a-possible-therapeutic-target
#1
Icard Philippe, Lincet Hubert
Proliferating cells reduce their oxidative metabolism and rely more on glycolysis, even in the presence of O2 (Warburg effect). This shift in metabolism reduces citrate biosynthesis and diminishes intracellular acidity, both of which promote glycolysis sustaining tumor growth. Because citrate is the donor of acetyl-CoA, its reduced production favors a deacetylation state of proteins favoring resistance to apoptosis and epigenetic changes, both processes contributing to tumor aggressiveness. Citrate levels could be monitored as an indicator of cancer aggressiveness (as already shown in human prostate cancer) and/or could serve as a biomarker for response to therapy...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27911865/mitochondrial-pyruvate-carrier-function-is-negatively-linked-to-warburg-phenotype-in-vitro-and-malignant-features-in-esophageal-squamous-cell-carcinomas
#2
Yaqing Li, Xiaoran Li, Quancheng Kan, Mingzhi Zhang, Xiaoli Li, Ruiping Xu, Junsheng Wang, Dandan Yu, Mariusz Adam Goscinski, Jian-Guo Wen, Jahn M Nesland, Zhenhe Suo
Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this study, we investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as aggressive features of esophageal squamous carcinoma. It was found that blocking pyruvate transportation into mitochondria attenuated mitochondrial oxidative phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg effect. In addition, the HIF-1α expression and ROS production were also activated upon UK5099 application...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911861/pyruvate-kinase-m2-pkm2-expression-correlates-with-prognosis-in-solid-cancers-a-meta-analysis
#3
Haiyan Zhu, Hui Luo, Xuejie Zhu, Xiaoli Hu, Lihong Zheng, Xueqiong Zhu
Pyruvate kinase M2 (PKM2) is the key enzyme in the Warburg effect and plays a central role in cancer cell metabolic reprogramming. Recently, quite a few studies have investigated the correlation between PKM2 expression and prognosis in multiple cancer patients, but results were inconsistent. We therefore performed a meta-analysis to explore the prognostic value of PKM2 expression in patients with solid cancer. Here twenty-seven individual studies from 25 publications with a total of 4796 cases were included to explore the association between PKM2 and overall survival (OS) or disease-free survival (DFS)/ progression-free survival (PFS)/ recurrent-free survival (RFS) in subjects with solid cancer...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911732/the-warburg-effect-80-years-on
#4
REVIEW
Michelle Potter, Emma Newport, Karl J Morten
Influential research by Warburg and Cori in the 1920s ignited interest in how cancer cells' energy generation is different from that of normal cells. They observed high glucose consumption and large amounts of lactate excretion from cancer cells compared with normal cells, which oxidised glucose using mitochondria. It was therefore assumed that cancer cells were generating energy using glycolysis rather than mitochondrial oxidative phosphorylation, and that the mitochondria were dysfunctional. Advances in research techniques since then have shown the mitochondria in cancer cells to be functional across a range of tumour types...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911436/uncovering-molecular-abnormalities-leading-to-the-warburg-effect-in-primary-refractory-diffuse-large-b-cell-lymphoma
#5
M Soleja, M Mims, G Rivero
No abstract text is available yet for this article.
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27900024/acute-effect-of-lactic-acid-on-tumor-endothelial-cell-metabolic-coupling-in-the-tumor-microenvironment
#6
Guanqun Zhu, Degui Wang, Shenqian Li, Xuecheng Yang, Yanwei Cao, Yonghua Wang, Haitao Niu
The present study aimed to systematically analyze alterations in the expression of mitochondrial-associated proteins in human bladder cancer T24 cells co-cultured with tumor-associated human umbilical vein endothelial cells (HUVECs), and to investigate the characteristics of bladder cancer cell energy metabolism. The present study used the following techniques: A co-culture system of T24 cells and HUVECs was constructed using a microfluidic chip as a 3D co-culture system; the concentration of lactic acid in the medium of the cells was determined using an automatic microplate reader; a qualitative analysis of mitochondria-associated protein expression was performed by immunofluorescent staining; and a quantitative analysis of mitochondrial-associated protein expression was conducted using western blotting...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895313/repurposing-the-anti-malarial-drug-dihydroartemisinin-suppresses-metastasis-of-non-small-cell-lung-cancer-via-inhibiting-nf-%C3%AE%C2%BAb-glut1-axis
#7
Jie Jiang, Guojun Geng, Xiuyi Yu, Hongming Liu, Jing Gao, Hanxiang An, Chengfu Cai, Ning Li, Dongyan Shen, Xiaoqiang Wu, Lisheng Zheng, Yanjun Mi, Shuyu Yang
Non-small-cell lung cancer (NSCLC) is an aggressive malignancy and long-term survival remains unsatisfactory for patients with metastatic and recurrent disease. Repurposing the anti-malarial drug dihydroartemisinin (DHA) has been proved to possess potent antitumor effect on various cancers. However, the effects of DHA in preventing the invasion of NSCLC cells have not been studied. In the present study, we determined the inhibitory effects of DHA on invasion and migration and the possible mechanisms involved using A549 and H1975 cells...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889643/multimodality-imaging-identifies-distinct-metabolic-profiles-in-vitro-and-in-vivo
#8
Marie-Aline Neveu, Géraldine De Preter, Valérie Marchand, Anne Bol, Jeffery R Brender, Keita Saito, Shun Kishimoto, Paolo E Porporato, Pierre Sonveaux, Vincent Grégoire, Olivier Feron, Bénédicte F Jordan, Murali C Krishna, Bernard Gallez
The study of alterations of tumor metabolism should allow the identification of new targets for innovative anticancer strategies. Metabolic alterations are generally established in vitro, and conclusions are often extrapolated to the in vivo situation without further tumor metabolic phenotyping. To highlight the key role of microenvironment on tumor metabolism, we studied the response of glycolytic and oxidative tumor models to metabolic modulations in vitro and in vivo. MDA-MB-231 and SiHa tumor models, characterized in vitro as glycolytic and oxidative, respectively, were studied...
November 24, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27883057/the-warburg-effect-mediator-pyruvate-kinase-m2-expression-and-regulation-in-the-retina
#9
Raju V S Rajala, Ammaji Rajala, Christopher Kooker, Yuhong Wang, Robert E Anderson
The tumor form of pyruvate kinase M2 (PKM2) undergoes tyrosine phosphorylation and gives rise to the Warburg effect. The Warburg effect defines a pro-oncogenic metabolism switch such that cancer cells take up more glucose than normal tissue and favor incomplete oxidation of glucose, even in the presence of oxygen. Retinal photoreceptors are highly metabolic and their energy consumption is equivalent to that of a multiplying tumor cell. In the present study, we found that PKM2 is the predominant isoform in both rod- and cone-dominant retina, and that it undergoes a light-dependent tyrosine phosphorylation...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27878287/pdk1-promotes-tumor-cell-proliferation-and-migration-by-enhancing-the-warburg-effect-in-non-small-cell-lung-cancer
#10
Tao Liu, Honglei Yin
Tumor cells prefer glycolysis (Warburg effect) during the proliferation and metastasis. The precise mechanism remains largely unknown. Here, we demonstrated that pyruvate dehydrogenase kinase 1 (PDK1) was a critical enzyme that functioned as an oncogene to promote non-small cell lung cancer (NSCLC) growth and metastasis. We discovered that PDK1 expression was significantly upregulated in NSCLC tissues and correlated with advanced T stage. Moreover, high expression of PDK1 was an independent prognostic factor of NSCLC...
November 16, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27878249/ets-1-a-potential-target-of-glycolysis-for-metabolic-therapy-by-regulating-glucose-metabolism-in-pancreatic-cancer
#11
Xiu Zhang, Dan Wu, Mohanad Aldarouish, Xiaodong Yin, Chunyan Li, Cailian Wang
Pancreatic cancer is one of the most lethal malignancies of all types of cancer due to lack of early symptoms and its resistance to conventional therapy. In our previous study, we have shown that v‑ets erythroblastosis virus E26 oncogene homolog‑1 (ETS‑1) promote cell migration and invasion in pancreatic cancer cells. However, the function of ETS‑1 in regulation of glycolysis and autophagy during progression of pancreatic cancer has not been defined yet. In this study, we sought to identify the potential role for silencing ETS‑1 in reducing the expression of glucose transporter‑1 (GLUT‑1) to disturb glycolysis through alteration of 'Warburg effect', by which could result in AMP‑activated protein kinase (AMPK) activation, autophagy induction and reduction of cell viability...
November 16, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27867011/tetrameric-acetyl-coa-acetyltransferase-1-is-important-for-tumor-growth
#12
Jun Fan, Ruiting Lin, Siyuan Xia, Dong Chen, Shannon E Elf, Shuangping Liu, Yaozhu Pan, Haidong Xu, Zhiyu Qian, Mei Wang, Changliang Shan, Lu Zhou, Qun-Ying Lei, Yuancheng Li, Hui Mao, Benjamin H Lee, Jessica Sudderth, Ralph J DeBerardinis, Guojing Zhang, Taofeek Owonikoko, Manila Gaddh, Martha L Arellano, Hanna J Khoury, Fadlo R Khuri, Sumin Kang, Paul W Doetsch, Sagar Lonial, Titus J Boggon, Walter J Curran, Jing Chen
Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) regulates pyruvate dehydrogenase complex (PDC) by acetylating pyruvate dehydrogenase (PDH) and PDH phosphatase. How ACAT1 is "hijacked" to contribute to the Warburg effect in human cancer remains unclear. We found that active, tetrameric ACAT1 is commonly upregulated in cells stimulated by EGF and in diverse human cancer cells, where ACAT1 tetramers, but not monomers, are phosphorylated and stabilized by enhanced Y407 phosphorylation. Moreover, we identified arecoline hydrobromide (AH) as a covalent ACAT1 inhibitor that binds to and disrupts only ACAT1 tetramers...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27864740/expression-levels-of-warburg-effect-related-micrornas-correlate-with-each-other-and-that-of-histone-deacetylase-enzymes-in-adult-hematological-malignancies-with-emphasis-on-acute-myeloid-leukemia
#13
Zsuzsanna Gaál, Éva Oláh, László Rejtő, Bálint László Bálint, László Csernoch
Disruption of epigenetic regulation and characteristic metabolic alterations (known as the Warburg-effect) are well-known hallmarks of cancer. In our study we investigated the expression levels of microRNAs and histone deacetylase enzymes via RT-qPCR in bone marrow specimens of adult patients suffering from hematological malignancies (total cohort n = 40), especially acute myeloid leukemia (n = 27). The levels of the three examined Warburg-effect related microRNAs (miR-378*, miR-23b, miR-26a) positively correlated with each other and the oncogenic miR-155 and miR-125b, while negatively with the level of the tumorsuppressor miR-124...
November 18, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27863025/decision-to-grow-or-to-invade-is-at-the-flick-of-metabolic-switch-pgc1%C3%AE
#14
Kristen S Hill, Minjung Kim
Cancer cells constantly reprogram their metabolism to meet anabolic and catabolic demands in real time. Increased aerobic glycolysis (the Warburg effect) is associated with highly proliferative tumors, since it confers several advantages to proliferating tumor cells by providing rapid ATP production from glycolysis and macromolecules (building blocks) for cell division. On the other hand, mitochondria-dependent oxidative phosphorylation (OxPhos) generates the maximal amount of ATP from glucose. Although underappreciated, OxPhos is also utilized to support growth of cancer cells, especially for "oxidative tumors" such as lymphomas, glioblastomas, and melanomas...
November 10, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27852038/transcriptomic-metabolomic-reprogramming-in-egfr-mutant-nsclc-early-adaptive-drug-escape-linking-tgf%C3%AE-2-bioenergetics-mitochondrial-priming
#15
Praveena S Thiagarajan, Xiaoliang Wu, Wei Zhang, Ivy Shi, Rakesh Bagai, Patrick Leahy, Yan Feng, Martina Veigl, Daniel Lindner, David Danielpour, Lihong Yin, Rafael Rosell, Trever G Bivona, Zhenfeng Zhang, Patrick C Ma
The impact of EGFR-mutant NSCLC precision therapy is limited by acquired resistance despite initial excellent response. Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy. Here, we characterized a novel non-mutational early adaptive drug-escape in EGFR-mutant lung tumor cells only days after therapy initiation, that is MET-independent. The drug-escape cell states were analyzed by integrated transcriptomic and metabolomics profiling uncovering a central role for autocrine TGFβ2 in mediating cellular plasticity through profound cellular adaptive Omics reprogramming, with common mechanistic link to prosurvival mitochondrial priming...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27851921/vhl-brings-warburg-into-the-memory-spotlight
#16
Greg M Delgoffe
Previous studies suggest mitochondrial metabolic pathways are essential for the generation of memory T cells. In this issue of Immunity, Phan et al. (2016) describe the formation of memory in T cells with constitutive glycolytic metabolism, suggesting that fuel does not necessarily dictate function.
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27843485/learning-latent-variable-gaussian-graphical-model-for-biomolecular-network-with-low-sample-complexity
#17
Yanbo Wang, Quan Liu, Bo Yuan
Learning a Gaussian graphical model with latent variables is ill posed when there is insufficient sample complexity, thus having to be appropriately regularized. A common choice is convex ℓ1 plus nuclear norm to regularize the searching process. However, the best estimator performance is not always achieved with these additive convex regularizations, especially when the sample complexity is low. In this paper, we consider a concave additive regularization which does not require the strong irrepresentable condition...
2016: Computational and Mathematical Methods in Medicine
https://www.readbyqxmd.com/read/27842912/upregulation-of-slc2-glut-family-genes-is-related-to-poor-survival-outcomes-in-papillary-thyroid-carcinoma-analysis-of-data-from-the-cancer-genome-atlas
#18
Young Jun Chai, Jin Wook Yi, So Won Oh, Young A Kim, Ka Hee Yi, Ju Han Kim, Kyu Eun Lee
BACKGROUND: The Warburg effect describes increased glucose uptake in cancer cells, and glucose transporter proteins are overexpressed in many tumors. In this study, we evaluated the expression of 14 SLC2A genes encoding glucose transporter proteins in papillary thyroid carcinoma patients. METHODS: Clinical information and gene expression data from 499 papillary thyroid carcinoma patients were downloaded from The Cancer Genome Atlas database. Correlations between SLC2 gene family (SLC2A1-14) mRNA expression levels and clinicopathologic factors were analyzed...
November 11, 2016: Surgery
https://www.readbyqxmd.com/read/27829133/lactate-wreaks-havoc-on-tumor-infiltrating-t-and-nk-cells
#19
Kristen E N Scott, John L Cleveland
Both cancer cells and activated T and NK immune cells display enhanced nutrient uptake and metabolism characteristic of the Warburg phenotype. In this issue of Cell Metabolism, Brand et al. (2016) demonstrate that cancer cell LDHA-derived lactic acid selectively disables T and NK cell activation and tumor immune surveillance.
November 8, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27824574/a-pilot-study-into-the-use-of-fdg-mnp-as-an-alternative-approach-in-neuroblastoma-cell-hyperthermia
#20
Mahendran Subramanian, Gillian Pearce, Ozge Kozgus Guldu, Volkan Tekin, Arkadiusz Miaskowski, Omer Aras, Perihan Unak
Herein, we present a pilot study concerning the use of fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNP) as a potential agent in magnetic nanoparticle mediated neuroblastoma cancer cell hyperthermia. This approach makes use of the 'Warburg effect', utilizing the fact that cancer cells have a higher metabolic rate than normal cells. FDG-mNP were synthesized, then applied to the SH-SY5Y neuroblastoma cancer cell line and exposed to an ac magnetic field. 3D Calorimetry was performed on the FDG-mNP compound...
September 2016: IEEE Transactions on Nanobioscience
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