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Jian Lu, Min Chen, Sumeng Gao, Jigang Yuan, Zhu Zhu, Xiaoping Zou
The 'Warburg effect' is considered a vital hallmark of cancer cells, characterized by an altered metabolism, in which cells rely on aerobic glycolysis. As a key enzyme of aerobic glycolysis, pyruvate kinase M2 (PKM2) serves a crucial role in tumorigenesis. Accumulating studies have indicated that PKM2 is a potential target for cancer therapy. The aim of the present study was to assess the anticancer effects of LY294002, a specific phosphatidylinositol-3-kinase inhibitor, on gastric cancer (GC) cells and further explore its possible mechanism in vitro ...
April 2018: Oncology Letters
Thenappan Thenappan, Mark L Ormiston, John J Ryan, Stephen L Archer
Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells...
March 14, 2018: BMJ: British Medical Journal
Dongya Jia, Jun Hyoung Park, Kwang Hwa Jung, Herbert Levine, Benny Abraham Kaipparettu
Aerobic glycolysis, also referred to as the Warburg effect, has been regarded as the dominant metabolic phenotype in cancer cells for a long time. More recently, it has been shown that mitochondria in most tumors are not defective in their ability to carry out oxidative phosphorylation (OXPHOS). Instead, in highly aggressive cancer cells, mitochondrial energy pathways are reprogrammed to meet the challenges of high energy demand, better utilization of available fuels and macromolecular synthesis for rapid cell division and migration...
March 13, 2018: Cells
Shu-Jie Zhao, Yi-Fei Shen, Qing Li, Yun-Jie He, Yun-Kun Zhang, Li-Peng Hu, Yu-Qing Jiang, Nan-Wei Xu, Yu-Ji Wang, Jun Li, Ya-Hui Wang, Fei Liu, Rong Zhang, Guo-Yong Yin, Jin-Hai Tang, Dong Zhou, Zhi-Gang Zhang
Cellular metabolic reprogramming is the main characteristic of cancer cells and identification of targets using this metabolic pattern is extremely important to treat cancers, such as osteosarcoma (OS). In this study, SLIT2 and ROBO1 were upregulated in OS, and higher expression of ROBO1 was associated with worse overall survival rate. Furthermore, in vitro and in vivo experiments demonstrated that the SLIT2/ROBO1 axis promotes proliferation, inhibits apoptosis, and contributes to the Warburg effect in OS cells...
March 9, 2018: Cell Death & Disease
Amy F Martinez, Samuel S McCachren, Marianne Lee, Helen A Murphy, Caigang Zhu, Brian T Crouch, Hannah L Martin, Alaattin Erkanli, Narasimhan Rajaram, Kathleen A Ashcraft, Andrew N Fontanella, Mark W Dewhirst, Nirmala Ramanujam
Many cancers adeptly modulate metabolism to thrive in fluctuating oxygen conditions; however, current tools fail to image metabolic and vascular endpoints at spatial resolutions needed to visualize these adaptations in vivo. We demonstrate a high-resolution intravital microscopy technique to quantify glucose uptake, mitochondrial membrane potential (MMP), and SO2 to characterize the in vivo phentoypes of three distinct murine breast cancer lines. Tetramethyl rhodamine, ethyl ester (TMRE) was thoroughly validated to report on MMP in normal and tumor-bearing mice...
March 8, 2018: Scientific Reports
Krzysztof Wrzesinski, Stephen J Fey
The recovery of physiological functionality, which is commonly seen in tissue mimetic three-dimensional (3D) cellular aggregates (organoids, spheroids, acini, etc.), has been observed in cells of many origins (primary tissues, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and immortal cell lines). This plurality and plasticity suggest that probably several basic principles promote this recovery process. The aim of this study was to identify these basic principles and describe how they are regulated so that they can be taken in consideration when micro-bioreactors are designed...
March 7, 2018: Bioengineering
Meng Zhang, Tingting Liu, Hui Sun, Weiwei Weng, Qiongyan Zhang, Chenchen Liu, Yang Han, Weiqi Sheng
Cancer cells metabolize glucose mainly by glycolysis and are well adapted to metabolic stress. Pim1 is an oncogene that promotes colorectal cancer (CRC) growth and metastasis, and its expression is positively correlated with CRC progression. However, the mechanism underlying Pim1 overexpression during CRC progression and the role of Pim1 in CRC metabolism remains unclear. In this study, we discovered that Pim1 expression was significantly upregulated in response to glucose deprivation-induced metabolic stress via AMPK signaling...
March 8, 2018: Cancer Science
Johannes C van der Mijn, Mathijs J Kuiper, Carl E H Siegert, Annabeth E Wassenaar, Carel J M van Noesel, Aernout C Ogilvie
Lactic acidosis is a commonly observed clinical condition that is associated with a poor prognosis, especially in malignancies. We describe a case of an 81-year-old patient who presented with symptoms of tachypnea and general discomfort. Arterial blood gas analysis showed a high anion gap acidosis with a lactate level of 9.5 mmol/L with respiratory compensation. CT scanning showed no signs of pulmonary embolism or other causes of impaired tissue oxygenation. Despite treatment with sodium bicarbonate, the patient developed an adrenalin-resistant cardiac arrest, most likely caused by the acidosis...
September 2017: Case Reports in Oncology
Elisabetta de Alteriis, Fabrizio Cartenì, Palma Parascandola, Jacinta Serpa, Stefano Mazzoleni
The mechanisms beyond the Warburg effect in proliferative mammalian cells, as well as for the similar Crabtree effect in the yeast Saccharomyces cerevisiae, are still a matter of debate: why do cells shift from the energy-efficient respiration to the energy-inefficient fermentation at high sugar concentration? This review reports on the strong similarities of these phenomena in both cell types, discusses the current ideas, and provides a novel interpretation of their common functional mechanism in a dynamic perspective...
March 6, 2018: Cell Cycle
Yannic Nonnenmacher, Karsten Hiller
In the last decade, metabolism has been recognized as a major determinant of immunological processes. During an inflammatory response, macrophages undergo striking changes in their metabolism. This metabolic reprogramming is governed by a complex interplay between metabolic enzymes and metabolites of different pathways and represents the basis for proper macrophage function. It is now evident that these changes go far beyond the well-known Warburg effect and the perturbation of metabolic targets is being investigated as a means to treat infections and auto-immune diseases...
March 3, 2018: Cellular and Molecular Life Sciences: CMLS
Antonietta Rosella Farina, Lucia Cappabianca, Luciana Gneo, Pierdomenico Ruggeri, Andrew Reay Mackay
Alternative TrkAIII splicing characterises advanced stage metastatic disease and post-therapeutic relapse in neuroblastoma (NB), and in NB models TrkAIII exhibits oncogenic activity. In this study, we report a novel role for TrkAIII in signaling ER stress to the mitochondria in SH-SY5Y NB cells that results in glycolytic metabolic adaptation. The ER stress-inducing agents DTT, A23187 and thapsigargin activated the ER stress-response in control pcDNA SH-SY5Y and TrkAIII expressing SH-SY5Y cells and in TrkAIII SH-SY5Y cells increased TrkAIII targeting to mitochondria and internalisation into inner-mitochondrial membranes...
February 2, 2018: Oncotarget
Michael D West, Ivan Labat, Hal Sternberg, Dana Larocca, Igor Nasonkin, Karen B Chapman, Ratnesh Singh, Eugene Makarev, Alex Aliper, Andrey Kazennov, Andrey Alekseenko, Nikolai Shuvalov, Evgenia Cheskidova, Aleksandr Alekseev, Artem Artemov, Evgeny Putin, Polina Mamoshina, Nikita Pryanichnikov, Jacob Larocca, Karen Copeland, Evgeny Izumchenko, Mikhail Korzinkin, Alex Zhavoronkov
Here we present the application of deep neural network (DNN) ensembles trained on transcriptomic data to identify the novel markers associated with the mammalian embryonic-fetal transition (EFT). Molecular markers of this process could provide important insights into regulatory mechanisms of normal development, epimorphic tissue regeneration and cancer. Subsequent analysis of the most significant genes behind the DNNs classifier on an independent dataset of adult-derived and human embryonic stem cell (hESC)-derived progenitor cell lines led to the identification of COX7A1 gene as a potential EFT marker...
January 30, 2018: Oncotarget
Dehua Tang, Lei Xu, Mingming Zhang, Robert Gregory Dorfman, Yida Pan, Qian Zhou, Lixing Zhou, Yuming Wang, Yang Li, Yuyao Yin, Lei Wang, Xiaoping Zou
Cholangiocarcinoma (CCA) is a highly lethal malignancy with an often late diagnosis and consequent poor prognosis. Chemotherapy is the only therapeutic strategy for most patients. Compared to normal cells, tumor cells preferentially metabolize glucose to lactate, even in aerobic conditions. Such metabolic alterations not only support the growth and invasion of tumor cells, but also promote their chemoresistance. The purpose of our study was to explore the role of metformin in regulating the metabolism of CCA, as well as to investigate whether metformin could act as a chemosensitizer of the HDAC3 inhibitor BG45, and therefore have potential for the treatment of CCA...
February 20, 2018: Oncology Reports
Lautaro Gándara, Pablo Wappner
In the last years, several reports have established the notion that metabolism is not just a housekeeping process, but instead an active effector of physiological changes. The idea that the metabolic status may rule a wide range of phenomena in cell biology is starting to be broadly accepted. Thus, current developmental biology has begun to describe different ways by which the metabolic profile of the cell and developmental programs of the organism can crosstalk. In this review, we discuss mechanisms by which metabolism impacts on processes governing development...
February 21, 2018: Mechanisms of Development
Xuelei Li, Dan Li, Dawei Song, Xixi Shi, Xu Tang, Hongzhou Zhang, Lianqi Zhang
To explore new serials of cathode materials with high electrochemical performance, the spinel-layered (1-x)[LiCrMnO4 ]·x[Li2 MnO3 ·LiCrO2 ] (x = 0, 0.25, 0.5, 0.75 and 1) composites are synthesized with sol-gel method. XRD, HRTEM, SAED and Raman spectra reveal that the structures of the (1-x)[LiCrMnO4 ]·x[Li2 MnO3 ·LiCrO2 ] cathode materials evolve from spinel to hybrid spinel-layered and layered structure with the increase of the Li concentration. Test results reveals that the structure and electrochemical performance of (1-x)[LiCrMnO4 ]·x[Li2 MnO3 ·LiCrO2 ] (x = 0...
February 22, 2018: ACS Applied Materials & Interfaces
Gopinath Prakasam, Mohammad Askandar Iqbal, Rameshwar N K Bamezai, Sybille Mazurek
Cancer cells rewire metabolism to meet biosynthetic and energetic demands. The characteristic increase in glycolysis, i.e., Warburg effect, now considered as a hallmark, supports cancer in various ways. To attain such metabolic reshuffle, cancer cells preferentially re-express the M2 isoform of pyruvate kinase (PKM2, M2-PK) and alter its quaternary structure to generate less-active PKM2 dimers. The relatively inactive dimers cause the accumulation of glycolytic intermediates that are redirected into anabolic pathways...
2018: Frontiers in Oncology
Lara P Fernández, Ricardo Ramos-Ruiz, Jesús Herranz, Roberto Martín-Hernández, Teodoro Vargas, Marta Mendiola, Laura Guerra, Guillermo Reglero, Jaime Feliu, Ana Ramírez de Molina
Metabolic alterations encountered in tumors are well recognized and considered as a hallmark of cancer. In addition to Warburg Effect, epidemiological and experimental studies support the crucial role of lipid metabolism in colorectal cancer (CRC). The overexpression of four lipid metabolism-related genes ( ABCA1, ACSL1, AGPAT1 and SCD genes) has been proposed as prognostic marker of stage II CRC (ColoLipidGene signature). In order to explore in depth the transcriptomic and genomic scenarios of ABCA1 , ACSL1 , AGPAT1 and SCD genes, we performed a transcriptomic meta-analysis in more than one thousand CRC individuals...
January 19, 2018: Oncotarget
Zhimin Lu, Tony Hunter
Protein kinases regulate every aspect of cellular activity, whereas metabolic enzymes are responsible for energy production and catabolic and anabolic processes. Emerging evidence demonstrates that some metabolic enzymes, such as pyruvate kinase M2 (PKM2), phosphoglycerate kinase 1 (PGK1), ketohexokinase (KHK) isoform A (KHK-A), hexokinase (HK), and nucleoside diphosphate kinase 1 and 2 (NME1/2), that phosphorylate soluble metabolites can also function as protein kinases and phosphorylate a variety of protein substrates to regulate the Warburg effect, gene expression, cell cycle progression and proliferation, apoptosis, autophagy, exosome secretion, T cell activation, iron transport, ion channel opening, and many other fundamental cellular functions...
February 17, 2018: Trends in Biochemical Sciences
Deyuan Fu, Jing Li, Jinli Wei, Zhengquan Zhang, Yulin Luo, Haosheng Tan, Chuanli Ren
BACKGROUND: High-mobility group box 2 (HMGB2) is implicated in tumorigenesis in various cancers. However, the clinical significance of HMGB2 signaling in human breast cancer progression remains unknown. METHODS: We investigated HMGB2 expression in 185 cases of primary breast cancer and matched normal breast tissue specimens, and explored the underlying mechanisms of altered HMGB2 expression as well as the impact of this altered expression on breast cancer growth and on aerobic glycolysis using in vitro and animal models of breast cancer...
February 20, 2018: Cell Communication and Signaling: CCS
Huiyuan Zhang, Qinyi Wang, Junzhong Gu, Le Yin, Shenghui Liang, Lida Wu, Hao Xu, Chao Zhao, Yuchun Gu
Warburg effect has been recognized as a hallmark of cancer cells for many years, but its modulation mechanism remains a great focus. Our current study found a member of solute carrier family 25 (SLC25A29), the main arginine transporter on mitochondria, significantly elevated in various cancer cells. Knockout of SLC25A29 by CRISPR/Cas9 inhibited proliferation and migration of cancer cells both in vitro and in vivo. SLC25A29-knockout cells also showed an altered metabolic status with enhanced mitochondrial respiration and reduced glycolysis...
February 20, 2018: Oncogene
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