MetaboList – May 2014

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Cancer metabolism
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Protein and Nucleotide Biosynthesis Are Coupled by a Single Rate-Limiting Enzyme, PRPS2, to Drive Cancer
John T. Cunningham, Melissa V. Moreno, Alessia Lodi, Sabrina M. Ronen, Davide Ruggero
http://www.cell.com/abstract/S0092-8674(14)00482-6

Targeting Lactate Dehydrogenase-A Inhibits Tumorigenesis and Tumor Progression in Mouse Models of Lung Cancer and Impacts Tumor-Initiating Cells
Han Xie, Jun-ichi Hanai, Jian-Guo Ren, Lev Kats, Kerri Burgess, Parul Bhargava, Sabina Signoretti, Julia Billiard, Kevin J. Duffy, Aaron Grant, Xiaoen Wang, Pawel K. Lorkiewicz, Sabrina Schatzman, Michael Bousamra, Andrew N. Lane, Richard M. Higashi, Teresa W.M. Fan, Pier Paolo Pandolfi, Vikas P. Sukhatme, Pankaj Seth
http://www.cell.com/cell-metabolism/abstract/S1550-4131(14)00107-7

A Mitochondrial RNAi Screen Defines Cellular Bioenergetic Determinants and Identifies an Adenylate Kinase as a Key Regulator of ATP Levels
Nathan J. Lanning, Brendan D. Looyenga, Audra L. Kauffman, Natalie M. Niemi, Jessica Sudderth, Ralph J. DeBerardinis, Jeffrey P. MacKeigan
http://www.cell.com/cell-reports/abstract/S2211-1247(14)00262-9

Serine, but Not Glycine, Supports One-Carbon Metabolism and Proliferation of Cancer Cells
Christiaan F. Labuschagne, Niels J.F. van den Broek, Gillian M. Mackay, Karen H. Vousden, Oliver D.K. Maddocks
http://www.cell.com/cell-reports/abstract/S2211-1247(14)00347-7

PTENα, a PTEN Isoform Translated through Alternative Initiation, Regulates Mitochondrial Function and Energy Metabolism
Hui Liang, Shiming He, Jingyi Yang, Xinying Jia, Pan Wang, Xi Chen, Zhong Zhang, Xiajuan Zou, Michael A. McNutt, Wen Hong Shen, Yuxin Yin
http://www.cell.com/cell-metabolism/abstract/S1550-4131(14)00128-4

IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism.
Grassian AR, Parker SJ, Davidson SM, Divakaruni AS, Green CR, Zhang X, Slocum KL, Pu M, Lin F, Vickers C, Joud-Caldwell C, Chung F, Yin H, Handly ED, Straub C, Growney JD, Vander Heiden MG, Murphy AN, Pagliarini R, Metallo CM.
http://cancerres.aacrjournals.org/content/early/2014/05/27/0008-5472.CAN-14-0772-T.abstract

Identification of anticancer drugs for hepatocellular carcinoma through personalized genome-scale metabolic modeling
Rasmus Agren, Adil Mardinoglu, Anna Asplund, Caroline Kampf, Mathias Uhlen, Jens Nielsen
http://msb.embopress.org/content/10/3/721.long

The metabolic demands of cancer cells are coupled to their size and protein synthesis rates
Dolfi  SC, Chan  L, Qiu  J, Tedeschi  PM, Bertino  JR, Hirshfield  KM, Oltvai  ZN, Vazquez  A
http://www.cancerandmetabolism.com/content/1/1/20/abstract

Insulin Receptor Substrate-2 Mediated Phosphatidylinositol-3-kinase Signaling Selectively Inhibits Glycogen Synthase Kinase-3β to Regulate Aerobic Glycolysis
Justine Landis and Leslie M. Shaw
http://www.jbc.org/content/early/2014/05/08/jbc.M114.564070.abstract

Identification of LDH-A as a therapeutic target for cancer cell killing via (i) p53/NAD(H)-dependent and (ii) p53-independent pathways
S J Allison, J R P Knight, C Granchi, R Rani, F Minutolo, J Milner and R M Phillips
http://www.nature.com/oncsis/journal/v3/n5/abs/oncsis201416a.html

Regulation of the pentose phosphate pathway by an androgen receptor–mTOR-mediated mechanism and its role in prostate cancer cell growth
E Tsouko, A S Khan, M A White, J J Han, Y Shi, F A Merchant, M A Sharpe, L Xin and D E Frigo
http://www.nature.com/oncsis/journal/v3/n5/abs/oncsis201418a.html

β-alanine suppresses malignant breast epithelial cell aggressiveness through alterations in metabolism and cellular acidity in vitro.
Vaughan RA, Gannon NP, Garcia-Smith R, Licon-Munoz Y, Barberena MA, Bisoffi M, Trujillo KA.
http://www.molecular-cancer.com/content/13/1/14

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Cellular metabolism
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Quantitative flux analysis reveals folate-dependent NADPH production
Jing Fan, Jiangbin Ye, Jurre J. Kamphorst, Tomer Shlomi, Craig B. Thompson & Joshua D. Rabinowitz
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13236.html

Cyclin D1–Cdk4 controls glucose metabolism independently of cell cycle progression
Yoonjin Lee, John E. Dominy, Yoon Jong Choi, Michael Jurczak, Nicola Tolliday, Joao Paulo Camporez, Helen Chim, Ji-Hong Lim, Hai-Bin Ruan, Xiaoyong Yang, Francisca Vazquez, Piotr Sicinski, Gerald I. Shulman & Pere Puigserver
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13267.html

Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia
Isabel Saez, Jordi Duran, Christopher Sinadinos, Antoni Beltran, Oscar Yanes, María F Tevy, Carlos Martínez-Pons, Marco Milán and Joan J Guinovart
http://www.nature.com/jcbfm/journal/v34/n6/abs/jcbfm201433a.html

Crystal structure of the human glucose transporter GLUT1
Dong Deng, Chao Xu, Pengcheng Sun, Jianping Wu, Chuangye Yan, Mingxu Hu & Nieng Yan
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13306.html

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Hypoxia
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Hypoxia-Inducible Factor-1 Promotes Pancreatic Ductal Adenocarcinoma Invasion and Metastasis by Activating Transcription of the Actin-Bundling Protein Fascin
Xiao Zhao, Song Gao, He Ren, Wei Sun, Huan Zhang, Jianwei Sun, Shengyu Yang, and Jihui Hao
http://cancerres.aacrjournals.org/content/74/9/2455.abstract.html?etoc

PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation
Muhammad Zaeem Noman, Giacomo Desantis, Bassam Janji, Meriem Hasmim, Saoussen Karray, Philippe Dessen, Vincenzo Bronte, and Salem Chouaib
http://jem.rupress.org/content/211/5/781?etoc

Human Rhomboid Family-1 Suppresses Oxygen-Independent Degradation of Hypoxia-Inducible Factor-1α in Breast Cancer
Zhuan Zhou, Fangfang Liu, Zhi-Song Zhang, Feifei Shu, Yangyang Zheng, Li Fu, and Lu-Yuan Li
http://cancerres.aacrjournals.org/content/74/10/2719.abstract.html?etoc

In vivo modulation of hypoxia-inducible signaling by topographical helix mimetics
Brooke Bullock Lao, Ivan Grishagin, Hanah Mesallati, Thomas F. Brewer, Bogdan Z. Olenyuk, and Paramjit S. Arora
http://www.pnas.org/content/111/21/7531.abstract.html?etoc

DNMT3a epigenetic program regulates the HIF-2α oxygen-sensing pathway and the cellular response to hypoxia
Gabriel Lachance, James Uniacke, Timothy E. Audas, Chet E. Holterman, Aleksandra Franovic, Josianne Payette, and Stephen Lee
http://www.pnas.org/content/111/21/7783.abstract.html?etoc

HIF1α and HIF2α Exert Distinct Nutrient Preferences in Renal Cells.
Arreola A, Cowey CL, Coloff JL, Rathmell JC, Rathmell WK.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0098705

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Starvation
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The natural compound oblongifolin C inhibits autophagic flux and enhances antitumor efficacy of nutrient deprivation
Yuanzhi Lao, Gang Wan, Zhenyan Liu, Xiaoyu Wang, Ping Ruan, Wei Xu, Danqing Xu, Weidong Xie, Yaou Zhang, Hongxi Xu and Naihan Xu
https://www.landesbioscience.com/journals/autophagy/article/28034/

Involvement of autophagy in hypoxic-excitotoxic neuronal death
Vanessa Ginet, Amélie Spiehlmann, Coralie Rummel, Nikita Rudinskiy, Yulia Grishchuk, Ruth Luthi-Carter, Peter GH Clarke, Anita C Truttmann and Julien Puyal
http://dx.doi.org/10.4161/auto.28264

p27 protects metabolically-stressed cardiomyocytes from apoptosis by promoting autophagy
Xuetao Sun, Abdul Momen, Jun Wu, Hossein Noyan, Renke Li, Rüdiger von Harsdorf, and Mansoor Husain
http://www.jbc.org/content/early/2014/05/02/jbc.M113.542795.abstract

Glucose Deprivation Induces G2/M Transition-Arrest and Cell Death in N-GlcNAc2-Modified Protein-Producing Renal Carcinoma Cells
Takahiro Isono, Tokuhiro Chano, Asuka Kitamura, Takeshi Yuasa
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096168

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mTOR
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A Diverse Array of Cancer-Associated MTOR Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity
Brian C. Grabiner, Valentina Nardi, Kıvanç Birsoy, Richard Possemato, Kuang Shen, Sumi Sinha, Alexander Jordan, Andrew H. Beck, and David M. Sabatini
http://cancerdiscovery.aacrjournals.org/content/4/5/554.abstract.html?etoc

Activating mTOR Mutations in a Patient with an Extraordinary Response on a Phase I Trial of Everolimus and Pazopanib
Nikhil Wagle, Brian C. Grabiner, Eliezer M. Van Allen, Eran Hodis, Susanna Jacobus, Jeffrey G. Supko, Michelle Stewart, Toni K. Choueiri, Leena Gandhi, James M. Cleary, Aymen A. Elfiky, Mary Ellen Taplin, Edward C. Stack, Sabina Signoretti, Massimo Loda, Geoffrey I. Shapiro, David M. Sabatini, Eric S. Lander, Stacey B. Gabriel, Philip W. Kantoff, Levi A. Garraway, and Jonathan E. Rosenberg
http://cancerdiscovery.aacrjournals.org/content/4/5/546.abstract.html?etoc

Maintaining Glycogen Synthase Kinase-3 Activity Is Critical for mTOR Kinase Inhibitors to Inhibit Cancer Cell Growth
Junghui Koo, Ping Yue, Anthony A. Gal, Fadlo R. Khuri, and Shi-Yong Sun
http://cancerres.aacrjournals.org/content/74/9/2555.abstract.html?etoc

Rapamycin increases mitochondrial efficiency by mtDNA-dependent reprogramming of mitochondrial metabolism in Drosophila
Eugenia Villa-Cuesta, Marissa A. Holmbeck, and David M. Rand
http://jcs.biologists.org/content/127/10/2282.abstract.html?etoc

Estradiol promotes pentose phosphate pathway addiction and cell survival via reactivation of Akt in mTORC1 hyperactive cells
Y Sun, X Gu, E Zhang, M-A Park, A M Pereira, S Wang, T Morrison, C Li, J Blenis, V H Gerbaudo, E P Henske and J J Yu
http://www.nature.com/cddis/journal/v5/n5/abs/cddis2014204a.html

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AMPK
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The mammalian AMP-activated protein kinase complex mediates glucose regulation of gene expression in the yeast Saccharomyces cerevisiae
Ye Tian, Loubna Bendrioua, David Carmena, Raul Garcia-Salcedo, Peter Dahl, David Carling, Stefan Hohmann
http://www.sciencedirect.com/science/article/pii/S0014579314003251

A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: comparison with effects of contraction and other AMPK activators
Yu Chiang Lai, Samanta Kviklyte, Didier Vertommen, Louise Lantier, Marc Foretz, Benoît Viollet, Stefan Hallén and Mark H. Rider
http://www.biochemj.org/bj/460/bj4600363.htm

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Miscellaneous
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Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
Anila K. Madiraju, Derek M. Erion, Yasmeen Rahimi, Xian-Man Zhang, Demetrios T. Braddock, Ronald A. Albright, Brett J. Prigaro, John L. Wood, Sanjay Bhanot, Michael J. MacDonald, Michael J. Jurczak, Joao-Paulo Camporez, Hui-Young Lee, Gary W. Cline, Varman T. Samuel, Richard G. Kibbey & Gerald I. Shulman
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13270.html

Constant Growth Rate Can Be Supported by Decreasing Energy Flux and Increasing Aerobic Glycolysis
[yeast]
Nikolai Slavov, Bogdan A. Budnik, David Schwab, Edoardo M. Airoldi, Alexander van Oudenaarden
http://www.cell.com/cell-reports/abstract/S2211-1247(14)00254-X

The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR
[nematode]
Randall M. Chin, Xudong Fu, Melody Y. Pai, Laurent Vergnes, Heejun Hwang*, Gang Deng, Simon Diep, Brett Lomenick,Vijaykumar S. Meli, Gabriela C. Monsalve, Eileen Hu, Stephen A. Whelan, Jennifer X. Wang, Gwanghyun Jung,Gregory M. Solis, Farbod Fazlollahi, Chitrada Kaweeteerawat10, Austin Quach, Mahta Nili11, Abby S. Krall, Hilary A. Godwin,Helena R. Chang, Kym F. Faull, Feng Guo, Meisheng Jiang, Sunia A. Trauger, Alan Saghatelian, Daniel Braas, Heather R. Christofk, Catherine F. Clarke, Michael A. Teitell, Michael Petrascheck, Karen Reue, Michael E. Jung,Alison R. Frand & Jing Huang
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13264.html

Lipid Metabolism Signatures in NASH-Associated HCC — Letter
Sonja M. Kessler, Stephan Laggai, Ahmad Barghash, Volkhard Helms, and Alexandra K. Kiemer
http://cancerres.aacrjournals.org/content/74/10/2903.full.html?etoc

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Reviews
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Hypoxia and the extracellular matrix: drivers of tumour metastasis
Daniele M. Gilkes, Gregg L. Semenza & Denis Wirtz
http://www.nature.com/nrc/journal/v14/n6/abs/nrc3726.html?lang=en

Surviving Metabolic Stress: Of Mice (Squirrels) and Men
William N. Hait, Matthias Versele, and Jin-Ming Yang
http://cancerdiscovery.aacrjournals.org/content/4/6/646.abstract.html?etoc

Analytical metabolomics-based approaches to pancreatic cancer
Iole Maria Di Gangia, Urska Vrhovseka, Valerio Pazienzab, Fulvio Mattivia
http://www.sciencedirect.com/science/article/pii/S0165993614000053

A Fresh View of Glycolysis and Glucokinase Regulation: History and Current Status
Sigurd Lenzen
http://www.jbc.org/content/289/18/12189.long

Mitochondrial oxidative phosphorylation TRAP(1)ped in tumor cells
Andrea Rasola, Len Neckers, Didier Picard
http://www.cell.com/trends/cell-biology/abstract/S0962-8924%2814%2900050-6

The Pyruvate Dehydrogenase Complexes, Structure-based Function and Regulation
Mulchand S. Patel, Natalia S. Nemeria, William Furey, and Frank Jordan
http://www.jbc.org/content/early/2014/05/05/jbc.R114.563148.abstract


Methods in Enzymology: reviews and methods
“Conceptual Background and Bioenergetic/Mitochondrial Aspects of Oncometabolism”
http://www.sciencedirect.com/science/bookseries/00766879/542/supp/C
Includes:
– Preface: Oncometabolism: A New Field of Research with Profound Therapeutic Implications
Lorenzo Galluzzi, Guido Kroemer
– The Metabolic Alterations of Cancer Cells
Marco Sciacovelli, Edoardo Gaude, Mika Hilvo, Christian Frezza
– Autophagy and Cancer Metabolism
Juliet Goldsmith, Beth Levine, Jayanta Debnath
– Regulation of Cancer Metabolism by Oncogenes and Tumor Suppressors
Raffaella Iurlaro, Clara Lucía León-Annicchiarico, Cristina Muñoz-Pinedo
– Cross Talk Between Cell Death Regulation and Metabolism
Simone Fulda

– Techniques to Monitor Glycolysis
Tara TeSlaa, Michael A. Teitell
– Measurement of Enolase Activity in Cell Lysates
Keigo Fukano, Kazuhiro Kimura
– Extracellular Flux Analysis to Monitor Glycolytic Rates and Mitochondrial Oxygen Consumption
Martin Pelletier, Leah K. Billingham, Madhu Ramaswamy, Richard M. Siegel
– Conventional Techniques to Monitor Mitochondrial Oxygen Consumption
Hélène Simonnet, Arnaud Vigneron, Jacques Pouysségur
– Use of Safranin for the Assessment of Mitochondrial Membrane Potential by High-Resolution Respirometry and Fluorometry
Gerhard Krumschnabel, Andrea Eigentler, Mario Fasching, Erich Gnaiger
– Kinetic Analysis of Local Oxygenation and Respiratory Responses of Mammalian Cells Using Intracellular Oxygen-Sensitive Probes and Time-Resolved Fluorometry
Alexander V. Zhdanov, Ruslan I. Dmitriev, James Hynes, Dmitri B. Papkovsky
– Cell-Based Measurements of Mitochondrial Function in Human Subjects
Ju-Gyeong Kang, Ping-yuan Wang, Paul M. Hwang
– Use of Chemical Probes to Detect Mitochondrial ROS by Flow Cytometry and Spectrofluorometry
Jing Chen, Clayton E. Mathews
– Methods to Monitor ROS Production by Fluorescence Microscopy and Fluorometry
Aleksandra Wojtala, Massimo Bonora, Dominika Malinska, Paolo Pinton, Jerzy Duszynski, Mariusz R. Wieckowski
– Genetically Encoded Redox Sensors
Wai Kan Chiu, Atif Towheed, Michael J. Palladino
– Use of Genetically Encoded Sensors to Monitor Cytosolic ATP/ADP Ratio in Living Cells
Andrei I. Tarasov, Guy A. Rutter
– Methods to Monitor and Compare Mitochondrial and Glycolytic ATP Production
Simone Patergnani, Federica Baldassari, Elena De Marchi, Agnieszka Karkucinska-Wieckowska, Mariusz R. Wieckowski, Paolo Pinton
– Measurement of ADP–ATP Exchange in Relation to Mitochondrial Transmembrane Potential and Oxygen Consumption
Christos Chinopoulos, Gergely Kiss, Hibiki Kawamata, Anatoly A. Starkov
– Real-Time Assessment of the Metabolic Profile of Living Cells with Genetically Encoded NADH Sensors
Yuzheng Zhao, Yi Yang, Joseph Loscalzo
– 13C Isotope-Assisted Methods for Quantifying Glutamine Metabolism in Cancer Cells
Jie Zhang, Woo Suk Ahn, Paulo A. Gameiro, Mark A. Keibler, Zhe Zhang, Gregory Stephanopoulos
– Measurement of Fatty Acid Oxidation Rates in Animal Tissues and Cell Lines
Frank K. Huynh, Michelle F. Green, Timothy R. Koves, Matthew D. Hirschey
– Methods to Assess Lipid Accumulation in Cancer Cells
Jørgen Sikkeland, Yang Jin, Fahri Saatcioglu
– Analysis of Hypoxia-Induced Metabolic Reprogramming
Chendong Yang, Lei Jiang, Huafeng Zhang, Larissa A. Shimoda, Ralph J. DeBerardinis, Gregg L. Semenza

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Comments
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Metabolic Status Determines Cancer Cell Sensitivity to Low Glucose
http://cancerdiscovery.aacrjournals.org/content/4/5/506.1.abstract.html?etoc

SAICAR Binding Activates PKM2 Protein Kinase Activity
http://cancerdiscovery.aacrjournals.org/content/4/5/OF20.abstract.html?etoc

mtDNA-dependent metabolic effects of mTOR
http://jcs.biologists.org/content/127/10/e1006.full.html?etoc

Hypoxia: Micro changes
http://www.nature.com/nrc/journal/v14/n6/full/nrc3754.html

Mutant IDH2 Inhibitor Looks Promising in AML
http://cancerdiscovery.aacrjournals.org/content/4/6/OF9.abstract.html?etoc

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