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Warburg effect cancer

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https://www.readbyqxmd.com/read/29137386/mitochondrial-calcium-uniporter-as-a-target-of-microrna-340-and-promoter-of-metastasis-via-enhancing-the-warburg-effect
#1
Changhui Yu, Yuhao Wang, Jiawen Peng, Qiang Shen, Mimi Chen, Wei Tang, Xiumei Li, Chunqing Cai, Bin Wang, Shaoxi Cai, Xiaojing Meng, Fei Zou
Background: A shift from oxygen phosphorylation to aerobic glycolysis was known as the Warburg effect and a characteristic of cancer cell metabolism facilitating metastasis. Mitochondrial calcium uniporter (MCU), a key ion channel that mediates Ca(2+) uptake into mitochondria, was found to promote cancer progression and metastasis. However, its explicit role in shifting metabolism of breast cancer cells has not been defined. Methods: We evaluated MCU overexpression or knock-down on migration, invasion and glucose metabolismin breast cancer cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137232/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...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29129783/hypoxia-induced-mir-214-expression-promotes-tumour-cell-proliferation-and-migration-by-enhancing-the-warburg-effect-in-gastric-carcinoma-cells
#3
Liuqing Yang, Weijie Zhang, Yanbo Wang, Tianhui Zou, Bin Zhang, Yuanyuan Xu, Taohong Pang, Qingqing Hu, Min Chen, Lei Wang, Ying Lv, Kai Yin, Hongwei Liang, Xi Chen, Guifang Xu, Xiaoping Zou
miR-214 is an important oncomiRNA and is upregulated in various types of cancer, including gastric cancer. However, the molecular mechanism underlying the ectopic expression and function of miR-214 in gastric cancer is largely undefined. In this study, we found that miR-214 induces the Warburg effect and promotes the migration and proliferation of human gastric cancer cells. According to the mechanistic analysis, miR-214 expression is induced by environmental hypoxia, and miR-214 mediates hypoxia-induced functions...
November 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29129693/foxj1-promotes-bladder-cancer-cell-growth-and-regulates-warburg-effect
#4
Shaozhong Xian, Donghao Shang, Guangqi Kong, Ye Tian
Forkhead Box J1 (FOXJ1) which belongs to Fox gene family, plays complex and crucial roles in processes of development, organogenesis, regulation of the immune system, as well as progression of several malignancies. However, how FOXJ1 functions in bladder cancer remains unclear. Here, we report that FOXJ1 is upregulated in most bladder cancer patients, and predicts poor clinical outcomes. FOXJ1 facilitates bladder cancer cell proliferation and colony formation. FOXJ1 knockdown suppresses bladder tumor growth in nude mice...
November 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29120752/the-glycogen-shunt-maintains-glycolytic-homeostasis-and-the-warburg-effect-in-cancer
#5
REVIEW
Robert G Shulman, Douglas L Rothman
Despite many decades of study there is a lack of a quantitative explanation for the Warburg effect in cancer. We propose that the glycogen shunt, a pathway recently shown to be critical for cancer cell survival, may explain the excess lactate generation under aerobic conditions characteristic of the Warburg effect. The proposal is based on research on yeast and mammalian muscle and brain that demonstrates that the glycogen shunt functions to maintain homeostasis of glycolytic intermediates and ATP during large shifts in glucose supply or demand...
November 2017: Trends in Cancer
https://www.readbyqxmd.com/read/29117556/cdk8-kinase-activity-promotes-glycolysis
#6
Matthew D Galbraith, Zdenek Andrysik, Ahwan Pandey, Maria Hoh, Elizabeth A Bonner, Amanda A Hill, Kelly D Sullivan, Joaquín M Espinosa
Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancerous tissues. Despite its importance in cancer development, our understanding of mechanisms driving this form of metabolic reprogramming is incomplete. We report here an analysis of colorectal cancer cells engineered to carry a single point mutation in the active site of the Mediator-associated kinase CDK8, creating hypomorphic alleles sensitive to bulky ATP analogs. Transcriptome analysis revealed that CDK8 kinase activity is required for the expression of many components of the glycolytic cascade...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29114069/bag3-directly-stabilizes-hexokinase-2-mrna-and-promotes-aerobic-glycolysis-in-pancreatic-cancer-cells
#7
Ming-Xin An, Si Li, Han-Bing Yao, Chao Li, Jia-Mei Wang, Jia Sun, Xin-Yu Li, Xiao-Na Meng, Hua-Qin Wang
Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level...
November 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29109698/the-emerging-facets-of-non-cancerous-warburg-effect
#8
Alyaa M Abdel-Haleem, Nathan E Lewis, Neema Jamshidi, Katsuhiko Mineta, Xin Gao, Takashi Gojobori
The Warburg effect (WE), or aerobic glycolysis, is commonly recognized as a hallmark of cancer and has been extensively studied for potential anti-cancer therapeutics development. Beyond cancer, the WE plays an important role in many other cell types involved in immunity, angiogenesis, pluripotency, and infection by pathogens (e.g., malaria). Here, we review the WE in non-cancerous context as a "hallmark of rapid proliferation." We observe that the WE operates in rapidly dividing cells in normal and pathological states that are triggered by internal and external cues...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29109098/2-methoxyestradiol-reverses-the-pro-carcinogenic-effect-of-l-lactate-in-osteosarcoma-143b-cells
#9
REVIEW
Magdalena Gorska-Ponikowska, Alicja Kuban-Jankowska, Agnieszka Daca, Stephan Nussberger
BACKGROUND/AIM: According to the reverse Warburg effect, tumor cells may metabolize lactate as an energy source and shuttle L-lactate to neighboring cancer cells, adjacent stroma, and vascular endothelial cells, thus inducing metabolic reprogramming. An increased tumor L-lactate level strictly correlates with increased metastasis, tumor recurrence and a poor outcome. A potent anticancer agent that may act on L-lactate activated cells is 2-metoxyestradiol. Thus, the aim of the study was to evaluate whether a potent anticancer agent, 2-methoxyestradiol, is able to reverse L-lactate-induced metabolic reprogramming in osteosarcoma 143B cells...
November 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29103184/in-silico-evaluation-of-variable-ph-on-the-binding-of-epidermal-growth-factor-receptor-ectodomain-to-its-ligand-through-molecular-dynamics-simulation-in-tumors
#10
Inderpal Singh, Gurvinder Singh, Vijeshwar Verma, Shashank Singh, Ratna Chandra
Many aggressive and metastatic cancer cell types show Warburg Effect; therefore, it is a possible adaptation helping cancer cells to rapidly divide and utilize the glycolytic intermediates for biosynthesis of ribose sugars (for nucleotide biosynthesis), fatty acid synthesis (lipids for membrane synthesis), NADPH (cellular currency for reductive biosynthesis) and lactate. This in due course results in decrease of extracellular pH, leading to acidic tumor micro-environment. EGFR is a crucial cell surface signaling receptor implicated in cancer cell survival and progression...
November 4, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/29092451/primordial-oscillations-in-life-direct-observation-of-glycolytic-oscillations-in-individual-hela-cervical-cancer-cells
#11
Takashi Amemiya, Kenichi Shibata, Yoshihiro Itoh, Kiminori Itoh, Masatoshi Watanabe, Tomohiko Yamaguchi
We report the first direct observation of glycolytic oscillations in HeLa cervical cancer cells, which we regard as primordial oscillations preserved in living cells. HeLa cells starved of glucose or both glucose and serum exhibited glycolytic oscillations in nicotinamide adenine dinucleotide (NADH), exhibiting asynchronous intercellular behaviors. Also found were spatially homogeneous and inhomogeneous intracellular NADH oscillations in the individual cells. Our results demonstrate that starved HeLa cells may be induced to exhibit glycolytic oscillations by either high-uptake of glucose or the enhancement of a glycolytic pathway (Crabtree effect or the Warburg effect), or both...
October 2017: Chaos
https://www.readbyqxmd.com/read/29073069/intragenic-dna-methylation-and-boris-mediated-cancer-specific-splicing-contribute-to-the-warburg-effect
#12
Smriti Singh, Sathiya Pandi Narayanan, Kajal Biswas, Amit Gupta, Neha Ahuja, Sandhya Yadav, Rajendra Kumar Panday, Atul Samaiya, Shyam K Sharan, Sanjeev Shukla
Aberrant alternative splicing and epigenetic changes are both associated with various cancers, but epigenetic regulation of alternative splicing in cancer is largely unknown. Here we report that the intragenic DNA methylation-mediated binding of Brother of Regulator of Imprinted Sites (BORIS) at the alternative exon of Pyruvate Kinase (PKM) is associated with cancer-specific splicing that promotes the Warburg effect and breast cancer progression. Interestingly, the inhibition of DNA methylation, BORIS depletion, or CRISPR/Cas9-mediated deletion of the BORIS binding site leads to a splicing switch from cancer-specific PKM2 to normal PKM1 isoform...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29047090/metabolic-reprogramming-and-redox-signaling-in-pulmonary-hypertension
#13
Lydie Plecitá-Hlavatá, Angelo D'alessandro, Karim El Kasmi, Min Li, Hui Zhang, Petr Ježek, Kurt R Stenmark
Pulmonary hypertension is a complex disease of the pulmonary vasculature, which in severe cases terminates in right heart failure. Complex remodeling of pulmonary arteries comprises the central issue of its pathology. This includes extensive proliferation, apoptotic resistance and inflammation. As such, the molecular and cellular features of pulmonary hypertension resemble hallmark characteristics of cancer cell behavior. The vascular remodeling derives from significant metabolic changes in resident cells, which we describe in detail...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29045536/the-warburg-effect-persistence-of-stem-cell-metabolism-in-cancers-as-a-failure-of-differentiation
#14
M Riester, Q Xu, A Moreira, J Zheng, F Michor, R J Downey
BACKGROUND: Two recent observations regarding the Warburg effect are that (i) the metabolism of stem cells is constitutive ('aerobic') glycolysis while normal cellular differentiation involves a transition to oxidative phosphorylation and (ii) the degree of glucose uptake of a malignancy as imaged by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is associated with histologic measures of tumor differentiation. Combining these observations, we hypothesized that the high levels of glucose uptake observed in poorly differentiated cancers may reflect persistence of the glycolytic metabolism of stem cells in malignant cells that fail to fully differentiate...
October 13, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29030545/fructose-1-6-bisphosphate-couples-glycolytic-flux-to-activation-of-ras
#15
Ken Peeters, Frederik Van Leemputte, Baptiste Fischer, Beatriz M Bonini, Hector Quezada, Maksym Tsytlonok, Dorien Haesen, Ward Vanthienen, Nuno Bernardes, Carmen Bravo Gonzalez-Blas, Veerle Janssens, Peter Tompa, Wim Versées, Johan M Thevelein
Yeast and cancer cells share the unusual characteristic of favoring fermentation of sugar over respiration. We now reveal an evolutionary conserved mechanism linking fermentation to activation of Ras, a major regulator of cell proliferation in yeast and mammalian cells, and prime proto-oncogene product. A yeast mutant (tps1∆) with overactive influx of glucose into glycolysis and hyperaccumulation of Fru1,6bisP, shows hyperactivation of Ras, which causes its glucose growth defect by triggering apoptosis. Fru1,6bisP is a potent activator of Ras in permeabilized yeast cells, likely acting through Cdc25...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29029484/ybx1-promotes-tumor-growth-by-elevating-glycolysis-in-human-bladder-cancer
#16
Liuyu Xu, Hongyun Li, Longchao Wu, Shiming Huang
Aerobic glycolysis, also known as Warburg effect, is a key hallmark of cancers. The Y-box-binding protein 1 (YBX1) is a well-known oncoprotein implicated in multiple malignant phenotypes of cancers. Meanwhile, little is known about the oncogenic functions and mechanisms of YBX1 in bladder cancer. Based on gene set enrichment analysis (GSEA) of TCGA RNAseq data, we find that YBX1 was profoundly involved in the glycolysis part of glucose metabolism. Loss- and gain-of-function studies show that YBX1 can enhance glycolysis as revealed by expression of glycolytic enzymes, glucose uptake, lactate secretion and extracellular acidification rate (ECAR)...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29026202/loss-of-abhd5-promotes-the-aggressiveness-of-prostate-cancer-cells
#17
Guohua Chen, Guoli Zhou, Siddhesh Aras, Zhenhui He, Stephanie Lucas, Izabela Podgorski, Wael Skar, James G Granneman, Jian Wang
The accumulation of neutral lipids in intracellular lipid droplets has been associated with the formation and progression of many cancers, including prostate cancer (PCa). Alpha-beta Hydrolase Domain Containing 5 (ABHD5) is a key regulator of intracellular neutral lipids that has been recently identified as a tumor suppressor in colorectal cancer, yet its potential role in PCa has not been investigated. Through mining publicly accessible PCa gene expression datasets, we found that ABHD5 gene expression is markedly decreased in metastatic castration-resistant PCa (mCRPC) samples...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024608/erastin-like-anti-warburg-agents-prevent-mitochondrial-depolarization-induced-by-free-tubulin-and-decrease-lactate-formation-in-cancer-cells
#18
David N DeHart, John J Lemasters, Eduardo N Maldonado
In Warburg metabolism, suppression of mitochondrial metabolism contributes to a low cytosolic ATP/ADP ratio favoring enhanced aerobic glycolysis. Flux of metabolites across the mitochondrial outer membrane occurs through voltage-dependent anion channels (VDAC). In cancer cells, free dimeric tubulin induces VDAC closure and dynamically regulates mitochondrial membrane potential (ΔΨ). Erastin, a small molecule that binds to VDAC, antagonizes the inhibitory effect of tubulin on VDAC and hyperpolarizes mitochondria in intact cells...
September 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28985623/maintenance-of-cellular-respiration-indicates-drug-resistance-in-acute-myeloid-leukemia
#19
Katharina Henkenius, Brandon H Greene, Christina Barckhausen, Raimo Hartmann, Melanie Märken, Tom Kaiser, Miriam Rehberger, Stephan K Metzelder, Wolfgang J Parak, Andreas Neubauer, Cornelia Brendel, Elisabeth Mack
Primary resistance to induction therapy is an unsolved clinical problem in acute myeloid leukemia (AML). Here we investigated drug resistance in AML at the level of cellular metabolism in order to identify early predictors of therapeutic response. Using extracellular flux analysis, we compared metabolic drug responses in AML cell lines sensitive or resistant to cytarabine or sorafenib after 24h of drug treatment to a small cell lung cancer (SCLC) cell line exposed to etoposide. Only drug-resistant AML cells maintained oxidative metabolism upon drug exposure while SCLC cells displayed an overall metabolic shift towards glycolysis, i...
November 2017: Leukemia Research
https://www.readbyqxmd.com/read/28983605/ldha-promotes-tumor-metastasis-by-facilitating-epithelial%C3%A2-mesenchymal-transition-in-renal-cell-carcinoma
#20
Juping Zhao, Xin Huang, Zhaoping Xu, Jun Dai, Hongchao He, Yu Zhu, Haofei Wang
Previous studies have indicated that high expression of lactate dehydrogenase A (LDHA) exists in many human cancers. Recently, several reports showed that silencing or inhibition of LDHA could suppress metastasis of human cancer including renal cell carcinoma (RCC). However, the mechanism remains unknown. The role of LDHA in RCC migration and invasion was investigated using immunohistochemistry, western blotting, Transwell and scratch assays, and in vivo experiment. The influence of LDHA on the Warburg effect was also investigated by LDHA activity and lactate production assay...
December 2017: Molecular Medicine Reports
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