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Warburg effect cancer

Yuanyuan Zhou, Xia Zheng, Jiaojiao Lu, Wei Chen, Xu Li, Le Zhao
BACKGROUND/AIMS: The Warburg effect is one of the main energy metabolism features supporting cancer cell growth. 20(S)-Rg3 exerts anti-tumor effect on ovarian cancer partly by inhibiting the Warburg effect. microRNAs are important regulators of the Warburg effect. However, the microRNA regulatory network mediating the anti-Warburg effect of 20(S)-Rg3 was largely unknown. METHODS: microRNA deep sequencing was performed to identify the 20(S)-Rg3-influenced microRNAs in SKOV3 ovarian cancer cells...
March 16, 2018: Cellular Physiology and Biochemistry
Diana Fang, Eduardo N Maldonado
Cancer metabolism is emerging as a chemotherapeutic target. Enhanced glycolysis and suppression of mitochondrial metabolism characterize the Warburg phenotype in cancer cells. The flux of respiratory substrates, ADP, and Pi into mitochondria and the release of mitochondrial ATP to the cytosol occur through voltage-dependent anion channels (VDACs) located in the mitochondrial outer membrane. Catabolism of respiratory substrates in the Krebs cycle generates NADH and FADH2 that enter the electron transport chain (ETC) to generate a proton motive force that maintains mitochondrial membrane potential (ΔΨ) and is utilized to generate ATP...
2018: Advances in Cancer Research
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
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
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
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
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
Ling Li, Yingchun Liang, Lei Kang, Yang Liu, Shan Gao, Siyu Chen, Ying Li, Wenye You, Qian Dong, Tian Hong, Zhifeng Yan, Shuai Jin, Tao Wang, Wei Zhao, Haixing Mai, Jun Huang, Xiao Han, Quanbo Ji, Qi Song, Chao Yang, Shixin Zhao, Xiaojie Xu, Qinong Ye
Aerobic glycolysis (the Warburg effect) facilitates tumor growth, and drugs targeting aerobic glycolysis are being developed. However, how the Warburg effect is directly regulated is largely unknown. Here we show that transcription factor SIX1 directly increases the expression of many glycolytic genes, promoting the Warburg effect and tumor growth in vitro and in vivo. SIX1 regulates glycolysis through HBO1 and AIB1 histone acetyltransferases. Cancer-related SIX1 mutation increases its ability to promote aerobic glycolysis and tumor growth...
February 8, 2018: Cancer Cell
Po-Lin Tseng, Wei-Hsuan Wu, Tsung-Hui Hu, Chih-Wei Chen, Hung-Chi Cheng, Chien-Feng Li, Wen-Hui Tsai, Hui-Ju Tsai, Meng-Che Hsieh, Jiin-Haur Chuang, Wen-Tsan Chang
Changes in TCA cycle enzymes or respiratory activity are possible mechanisms of aerobic glycolysis that contributes to tumor progression. To clarify whether the decrease of succinate dehydrogenase B (SDHB) alters energy metabolism, induces the Warburg effect and results in tumor malignancy, SDHB expression was examined and modulated in hepatocellular carcinoma (HCC) tissues and cells, respectively. SDHB level was often decreased in malignant HCC cells and tissues. Furthermore, the reduced SDHB expression was associated with advanced tumor stage and poor survival rate...
February 15, 2018: Scientific Reports
Sahithi Pamarthy, Arpita Kulshrestha, Gajendra K Katara, Kenneth D Beaman
The Vacuolar ATPase (V-ATPase) is a proton pump responsible for controlling the intracellular and extracellular pH of cells. The structure of V-ATPase has been highly conserved among all eukaryotic cells and is involved in diverse functions across species. V-ATPase is best known for its acidification of endosomes and lysosomes and is also important for luminal acidification of specialized cells. Several reports have suggested the involvement of V-ATPase in maintaining an alkaline intracellular and acidic extracellular pH thereby aiding in proliferation and metastasis of cancer cells respectively...
February 15, 2018: Molecular Cancer
Jihong Sun, Jingjing Li, Zhixian Guo, Lu Sun, Chenghui Juan, Yubing Zhou, Hongli Gu, Yan Yu, Qiuyue Hu, Quancheng' Kan, Zujiang Yu
Most cancers rely disproportionately on glycolysis for energy even in the presence of adequate oxygen supply, a condition known as "aerobic glycolysis", or the "Warburg effect". Pyruvate dehydrogenase E1a subunit (PDHA1) is one of main factors for metabolic switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis and has been suggested to be closely associated with tumorigenesis. Here we observed that PDHA1 protein was reduced in hepatocellular carcinoma (HCC) specimens by immunohistochemistry and western blot, which was significantly associated with poor overall survival...
February 14, 2018: Oncology Research
Ryo Yonashiro, Kayoko Eguchi, Masaki Wake, Norihiko Takeda, Koh Nakayama
Downregulation of pyruvate dehydrogenase (PDH) is critical for the aberrant preferential activation of glycolysis in cancer cells under normoxic conditions. Phosphorylation-dependent inhibition of PDH is a relevant event in this process, but it is not durable since it relies on PDH kinases which are activated ordinarily under hypoxic conditions. Thus, it remains unclear how PDH is durably downregulated in cancer cells that are not hypoxic. Building on evidence that PDH activity depends on the stability of a multi-protein PDH complex, we found that the PDH-E1β subunit of the PDH complex is downregulated to inhibit PDH activity under conditions of prolonged hypoxia...
February 7, 2018: Cancer Research
Roberto Serna-Blasco, Marta Sanz-Álvarez, Óscar Aguilera, Jesús García-Foncillas
RAS protein family members (KRAS4A, KRAS4B, HRAS and NRAS) function as GDP-GTP-regulated on-off switches, which regulate cytoplasmic-nuclear signaling networks ruling diverse normal cellular processes. Constitutive activating mutations in RAS genes are found in up to 30% of human cancers, and remarkably, the oncogenic Ras mutations and mutations in other components of Ras/MAPK signaling pathways seem to be mutually exclusive in most tumors, pointing out that deregulation of Ras-dependent signaling is an essential requirement for tumorigenesis...
February 9, 2018: Seminars in Cancer Biology
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