MetaboList – December 2015

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Starvation, mTOR, AMPK
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Sestrin2 is a leucine sensor for the mTORC1 pathway
Rachel L. Wolfson, Lynne Chantranupong, Robert A. Saxton, Kuang Shen, Sonia M. Scaria, Jason R. Cantor, David M. Sabatini
http://www.sciencemag.org/content/351/6268/43.full

Architecture of human mTOR complex 1
Christopher H. S. Aylett1, Evelyn Sauer, Stefan Imseng, Daniel Boehringer, Michael N. Hall, Nenad Ban, Timm Maier
http://www.sciencemag.org/content/351/6268/48.full

Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway
Robert A. Saxton, Kevin E. Knockenhauer, Rachel L. Wolfson, Lynne Chantranupong, Michael E. Pacold, Tim Wang, Thomas U. Schwartz, David M. Sabatini
http://www.sciencemag.org/content/351/6268/53.full

Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate functional domains
Hanseong Kim, Sojin An, Seung-Hyun Ro, Filipa Teixeira, Gyeong Jin Park, Cheal Kim, Chun-Seok Cho, Jeong-Sig Kim, Ursula Jakob, Jun Hee Lee and Uhn-Soo Cho
http://www.nature.com/ncomms/2015/151127/ncomms10025/full/ncomms10025.html

Drosophila Lipin interacts with insulin and TOR signaling pathways in the control of growth and lipid metabolism
Sandra Schmitt, Rupali Ugrankar, Stephanie E. Greene, Meenakshi Prajapati, and Michael Lehmann
http://jcs.biologists.org/content/128/23/4395.abstract?etoc

Starvation Induces Proteasome Autophagy with Different Pathways for Core and Regulatory Particle
Kenrick A. Waite, Alina De La Mota-Peynado, Gabrielle Vontz, and Jeroen Roelofs
http://www.jbc.org/content/early/2015/12/15/jbc.M115.699124.abstract
[yeast]

SUMOylation of AMPKα1 by PIAS4 specifically regulates mTORC1 signalling
Yan Yan, Saara Ollila, Iris P. L. Wong, Tea Vallenius, Jorma J. Palvimo, Kari Vaahtomeri and Tomi P. Mäkelä
http://www.nature.com/ncomms/2015/151130/ncomms9979/full/ncomms9979.html

AMPK-Dependent Phosphorylation of GAPDH Triggers Sirt1 Activation and Is Necessary for Autophagy upon Glucose Starvation
Chunmei Chang, Hua Su, Danhong Zhang, Yusha Wang, Qiuhong Shen, Bo Liu, Rui Huang, Tianhua Zhou, Chao Peng, Catherine C.L. Wong, Han-Ming Shen, Jennifer Lippincott-Schwartz, Wei Liu
http://www.cell.com/molecular-cell/abstract/S1097-2765(15)00828-X

Fyn-phosphorylated PIKE-A binds and inhibits AMPK signaling, blocking its tumor suppressive activity
S Zhang, Q Qi, C B Chan, W Zhou, J Chen, H R Luo, C Appin, D J Brat and K Ye
http://www.nature.com/cdd/journal/v23/n1/abs/cdd201566a.html

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Cancer metabolism
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The Genomic Landscape of Renal Oncocytoma Identifies a Metabolic Barrier to Tumorigenesis
Shilpy Joshi, Denis Tolkunov, Hana Aviv, Abraham A. Hakimi, Ming Yao, James J. Hsieh, Shridar Ganesan, Chang S. Chan, Eileen White
http://www.cell.com/cell-reports/abstract/S2211-1247(15)01248-6

NRF2 regulates serine biosynthesis in non-small cell lung cancer
Gina M DeNicola, Pei-Hsuan Chen, Edouard Mullarky, Jessica A Sudderth, Zeping Hu, David Wu, Hao Tang, Yang Xie, John M Asara, Kenneth E Huffman, Ignacio I Wistuba, John D Minna, Ralph J DeBerardinis & Lewis C Cantley
http://www.nature.com/ng/journal/v47/n12/full/ng.3421.html

Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization
Elias Björnson, Bani Mukhopadhyay, Anna Asplund, Nusa Pristovsek, Resat Cinar, Stefano Romeo, Mathias Uhlen, George Kunos, Jens Nielsen, Adil Mardinoglu
http://www.cell.com/cell-reports/abstract/S2211-1247(15)01215-2

Down-Regulation of NDUFB9 Promotes Breast Cancer Cell Proliferation, Metastasis by Mediating Mitochondrial Metabolism
Liang-Dong Li, He-Fen Sun, Xue-Xiao Liu, Shui-Ping Gao, Hong-Lin Jiang, Xin Hu, Wei Jin
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144441

Integration of tissue metabolomics, transcriptomics and immunohistochemistry reveals ERG- and gleason score- specific metabolomic alterations in prostate cancer
Sebastian Meller1, Hellmuth-A Meyer, Bianca Bethan, Dimo Dietrich, Sandra González Maldonado, Michael Lein, Matteo Montani, Regina Reszka, Philipp Schatz, Erik Peter, Carsten Stephan, Klaus Jung, Beate Kamlage, and Glen Kristiansen
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=6370&path%5B%5D=17415

Long Noncoding RNA Ceruloplasmin Promotes Cancer Growth by Altering Glycolysis
Rajesha Rupaimoole, Jaehyuk Lee, Monika Haemmerle, Hui Ling, Rebecca A. Previs, Sunila Pradeep, Sherry Y. Wu, Cristina Ivan, Manuela Ferracin, Jennifer B. Dennison, Niki M. Zacharias Millward, Archana S. Nagaraja, Kshipra M. Gharpure, Michael McGuire, Nidhin Sam, Guillermo N. Armaiz-Pena, Nouara C. Sadaoui, Cristian Rodriguez-Aguayo, George A. Calin, Ronny I. Drapkin, Jeffery Kovacs, Gordon B. Mills, Wei Zhang, Gabriel Lopez-Berestein, Pratip K. Bhattacharya, Anil K. Sood
http://www.cell.com/cell-reports/fulltext/S2211-1247(15)01362-5

Bonded Cumomer Analysis of Human Melanoma Metabolism Monitored by 13C NMR Spectroscopy of Perfused Tumor Cells
Alexander A. Shestov, Anthony Mancuso, Seung-Cheol Lee, Lili Guo, David S. Nelson, Jeffrey C. Roman, Pierre-Gilles Henry, Dennis B. Leeper, Ian A. Blair, and Jerry D. Glickson
http://www.jbc.org/content/early/2015/12/24/jbc.M115.701862.abstract

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IDH
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Insulator dysfunction and oncogene activation in IDH mutant gliomas
William A. Flavahan, Yotam Drier, Brian B. Liau, Shawn M. Gillespie, Andrew S. Venteicher, Anat O. Stemmer-Rachamimov, Mario L. Suvà & Bradley E. Bernstein
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature16490.html

Evidence that 2-hydroxyglutarate is not readily metabolized in colorectal carcinoma cells
Gelman S, Mahieu N, Cho K, Llufrio E, Wencewicz T, Patti G
http://www.cancerandmetabolism.com/content/3/1/13/abstract

Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents
Pu Wang, Jing Wu, Shenghong Ma, Lei Zhang, Jun Yao, Katherine A. Hoadley, Matthew D. Wilkerson, Charles M. Perou, Kun-Liang Guan, Dan Ye, Yue Xiong
http://www.cell.com/cell-reports/abstract/S2211-1247(15)01329-7

Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion
Kensuke Tateishi, Hiroaki Wakimoto, A. John Iafrate, Shota Tanaka, Franziska Loebel, Nina Lelic, Dmitri Wiederschain, Olivier Bedel, Gejing Deng, Bailin Zhang, Timothy He, Xu Shi, Robert E. Gerszten, Yiyun Zhang, Jing-Ruey J. Yeh, William T. Curry, Dan Zhao, Sudhandra Sundaram, Fares Nigim, Mara V.A. Koerner, Quan Ho, David E. Fisher, Elisabeth M. Roider, Lajos V. Kemeny, Yardena Samuels, Keith T. Flaherty, Tracy T. Batchelor, Andrew S. Chi, Daniel P. Cahill
http://www.cell.com/cancer-cell/abstract/S1535-6108(15)00427-4

Integrated genomic characterization of IDH1-mutant glioma malignant progression
Hanwen Bai, Akdes Serin Harmancı, E Zeynep Erson-Omay, Jie Li, Süleyman Coşkun, Matthias Simon, Boris Krischek, Koray Özduman, S Bülent Omay, Eric A Sorensen, Şevin Turcan, Mehmet Bakırcığlu, Geneive Carrión-Grant, Phillip B Murray, Victoria E Clark, A Gulhan Ercan-Sencicek, James Knight, Leman Sencar, Selin Altınok, Leon D Kaulen, Burcu Gülez, Marco Timmer, Johannes Schramm, Ketu Mishra-Gorur, Octavian Henegariu, Jennifer Moliterno, Angeliki Louvi, Timothy A Chan, Stacey L Tannheimer, M Necmettin Pamir, Alexander O Vortmeyer, Kaya Bilguvar, Katsuhito Yasuno & Murat Günel
http://www.nature.com/ng/journal/v48/n1/full/ng.3457.html

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Lipids
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Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling
Autumn G. York, Kevin J. Williams, Joseph P. Argus, Quan D. Zhou, Gurpreet Brar, Laurent Vergnes, Elizabeth E. Gray, Anjie Zhen, Nicholas C. Wu, Douglas H. Yamada, Cameron R. Cunningham, Elizabeth J. Tarling, Moses Q. Wilks, David Casero, David H. Gray, Amy K. Yu, Eric S. Wang, David G. Brooks, Ren Sun, Scott G. Kitchen, Ting-Ting Wu, Karen Reue, Daniel B. Stetson, Steven J. Bensinger
http://www.cell.com/cell/abstract/S0092-8674(15)01564-0

Obesity Contributes to Ovarian Cancer Metastatic Success through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages
Yueying Liu, Matthew N. Metzinger, Kyle A. Lewellen, Stephanie N. Cripps,Kyle D. Carey, Elizabeth I. Harper, Zonggao Shi, Laura Tarwater, Annie Grisoli, Eric Lee, Ania Slusarz, Jing Yang, Elizabeth A. Loughran, Kaitlyn Conley, Jeff J. Johnson, Yuliya Klymenko, Lana Bruney, Zhong Liang, Norman J. Dovichi, Bentley Cheatham, W. Matthew Leevy, and M. Sharon Stack
http://cancerres.aacrjournals.org/content/75/23/5046.abstract?etoc

Differential epigenetic reprogramming in response to specific endocrine therapies promotes cholesterol biosynthesis and cellular invasion
Van T. M. Nguyen, Iros Barozzi, Monica Faronato, Ylenia Lombardo, Jennifer H. Steel, Naina Patel, Philippa Darbre, Leandro Castellano, Balázs Győrffy, Laura Woodley, Alba Meira, Darren K. Patten, Valentina Vircillo, Manikandan Periyasamy, Simak Ali, Gianmaria Frige, Saverio Minucci, R. Charles Coombes and Luca Magnani
http://www.nature.com/ncomms/2015/151127/ncomms10044/full/ncomms10044.html

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Hypoxia and HIFs
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Hypoxia upregulates Rab11-family interacting protein 4 through HIF-1α to promote the metastasis of hepatocellular carcinoma
F Hu, X Deng, X Yang, H Jin, D Gu, X Lv, C Wang, Y Zhang, X Huo, Q Shen, Q Luo, F Zhao, T Ge, F Zhao, W Chu, H Shu, M Yao, J Fan and W Qin
http://www.nature.com/onc/journal/v34/n49/abs/onc201549a.html

The Immune-Metabolic Basis of Effector Memory CD4+ T Cell Function under Hypoxic Conditions
Sarah Dimeloe, Matthias Mehling, Corina Frick, Jordan Loeliger,Glenn R. Bantug, Ursula Sauder, Marco Fischer, Réka Belle, Leyla Develioglu, Savaş Tay, Anja Langenkamp and Christoph Hess
http://www.jimmunol.org/content/early/2015/11/27/jimmunol.1501766.abstract

Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer
Jun Yang, Alaa AlTahan, Dylan T. Jones, Francesca M. Buffa, Esther Bridges, Rodrigo B. Interiano, Chunxu Qu, Nathan Vogt, Ji-Liang Li, Dilair Baban, Jiannis Ragoussis, Robert Nicholson, Andrew M. Davidoff, and Adrian L. Harris
http://www.pnas.org/content/112/49/15172.abstract.html?etoc

Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1α upon LPS Activation in the Presence of Ample Oxygen
Isabel Siegert, Johannes Schödel, Manfred Nairz, Valentin Schatz, Katja Dettmer, Christopher Dick, Joanna Kalucka, Kristin Franke, Martin Ehrenschwender, Gunnar Schley, Angelika Beneke, Jörg Sutter, Matthias Moll, Claus Hellerbrand, Ben Wielockx, Dörthe M. Katschinski, Roland Lang, Bruno Galy, Matthias W. Hentze, Peppi Koivunen, Peter J. Oefner, Christian Bogdan, Günter Weiss, Carsten Willam, Jonathan Jantsch
http://www.cell.com/cell-reports/abstract/S2211-1247(15)01292-9

Hif-1α and Hif-2α synergize to suppress AML development but are dispensable for disease maintenance
Milica Vukovic, Amelie V. Guitart, Catarina Sepulveda, Arnaud Villacreces, Eoghan O’Duibhir, Theano I. Panagopoulou, Alasdair Ivens, Juan Menendez-Gonzalez, Juan Manuel Iglesias, Lewis Allen, Fokion Glykofrydis, Chithra Subramani, Alejandro Armesilla-Diaz, Annemarie E.M. Post, Katrin Schaak, Deniz Gezer, Chi Wai Eric So, Tessa L. Holyoake, Andrew Wood, Dónal O’Carroll, Peter J. Ratcliffe, and Kamil R. Kranc
http://jem.rupress.org/content/212/13/2223?etoc

Fumarate and Succinate Regulate Expression of Hypoxia-Inducible Genes via TET Enzymes
Tuomas Laukka, Christopher J. Mariani, Tuukka Ihantola, John Z. Cao, Juho Hokkanen, William G. Kaelin, Jr., Lucy A. Godley, and Peppi Koivunen
http://www.jbc.org/content/early/2015/12/23/jbc.M115.688762.abstract

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Anti-metabolic drugs
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Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH
Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, Roper J, Chio II, Giannopoulou EG, Rago C, Muley A, Asara JM, Paik J, Elemento O, Chen Z, Pappin DJ, Dow LE, Papadopoulos N, Gross SS, Cantley LC.
http://www.sciencemag.org/content/350/6266/1391.long

Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis
Takla Griss,Emma E. Vincent,Robert Egnatchik,Jocelyn Chen,Eric H. Ma,Brandon Faubert,Benoit Viollet,Ralph J. DeBerardinis,Russell G. Jones
http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002309

Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation
Jing Wang, Cheng Luo, Changliang Shan, Qiancheng You, Junyan Lu, Shannon Elf, Yu Zhou, Yi Wen, Jan L. Vinkenborg, Jun Fan, Heebum Kang, Ruiting Lin, Dali Han, Yuxin Xie, Jason Karpus, Shijie Chen, Shisheng Ouyang, Chihao Luan, Naixia Zhang, Hong Ding, Maarten Merkx, Hong Liu, Jing Chen, Hualiang Jiang & Chuan He
http://www.nature.com/nchem/journal/v7/n12/full/nchem.2381.html

Drug repurposing: sulfasalazine sensitizes gliomas to gamma knife radiosurgery by blocking cystine uptake through system Xc−, leading to glutathione depletion
L Sleire, B S Skeie, I A Netland, H E Førde, E Dodoo, F Selheim, L Leiss, J I Heggdal, P-H Pedersen, J Wang and P Ø Enger
http://www.nature.com/onc/journal/v34/n49/abs/onc201560a.html

Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic
Hai-nan Zhang, Lina Yang, Jian-ya Ling, Daniel M. Czajkowsky, Jing-Fang Wang, Xiao-Wei Zhang, Yi-Ming Zhou, Feng Ge, Ming-kun Yang, Qian Xiong, Shu-Juan Guo, Huang-Ying Le, Song-Fang Wu, Wei Yan, Bingya Liu, Heng Zhu, Zhu Chen, and Sheng-ce Tao
http://www.pnas.org/content/112/49/15084.abstract.html?etoc

2-deoxy-glucose down regulates endothelial AKT and ERK via interference with N-linked glycosylation, induction of endoplasmic reticulum stress and GSK-3B activation
Kovacs K, Decatur C, Toro M, Pham DG, Liu H, Jing Y, Murray TG, Lampidis TJ, Merchan JR.
http://mct.aacrjournals.org/content/early/2015/12/04/1535-7163.MCT-14-0315.long

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Miscellaneous
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Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction
Ende Zhao, Tomasz Maj, Ilona Kryczek, Wei Li, Ke Wu, Lili Zhao, Shuang Wei, Joel Crespo, Shanshan Wan, Linda Vatan, Wojciech Szeliga, Irene Shao, Yin Wang, Yan Liu, Sooryanarayana Varambally, Arul M Chinnaiyan, Theodore H Welling, Victor Marquez, Jan Kotarski, Hongbo Wang, Zehua Wang, Yi Zhang, Rebecca Liu, Guobin Wang & Weiping Zou
http://www.nature.com/ni/journal/v17/n1/full/ni.3313.html

MYC Disrupts the Circadian Clock and Metabolism in Cancer Cells
Brian J. Altman, Annie L. Hsieh, Arjun Sengupta, Saikumari Y. Krishnanaiah, Zachary E. Stine, Zandra E. Walton, Arvin M. Gouw, Anand Venkataraman, Bo Li, Pankuri Goraksha-Hicks, Sharon J. Diskin, David I. Bellovin, M. Celeste Simon, Jeffrey C. Rathmell, Mitchell A. Lazar, John M. Maris, Dean W. Felsher, John B. Hogenesch, Aalim M. Weljie, Chi V. Dang
http://www.cell.com/cell-metabolism/abstract/S1550-4131(15)00460-X

RICTOR Amplification Defines a Novel Subset of Patients with Lung Cancer Who May Benefit from Treatment with mTORC1/2 Inhibitors
Haiying Cheng, Yiyu Zou, Jeffrey S. Ross, Kai Wang, Xuewen Liu, Balazs Halmos, Siraj M. Ali, Huijie Liu, Amit Verma, Cristina Montagna, Abraham Chachoua, Sanjay Goel, Edward L. Schwartz, Changcheng Zhu, Jidong Shan, Yiting Yu, Kira Gritsman, Roman Yelensky, Doron Lipson, Geoff Otto, Matthew Hawryluk, Philip J. Stephens, Vincent A. Miller, Bilal Piperdi, and Roman Perez-Soler
http://cancerdiscovery.aacrjournals.org/content/5/12/1262.abstract?etoc

Mevalonate Pathway Regulates Cell Size Homeostasis and Proteostasis through Autophagy
Teemu P. Miettinen, Mikael Björklund
http://www.cell.com/cell-reports/abstract/S2211-1247(15)01360-1

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Reviews / previews
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Evidence of cancer-promoting roles for AMPK and related kinases
Tiziana Monteverde, Nathiya Muthalagu, Jennifer Port and Daniel J. Murphy
http://onlinelibrary.wiley.com/doi/10.1111/febs.13534/abstract

Pancreatic Cancer Metabolism: Breaking It Down to Build It Back Up
Rushika M. Perera and Nabeel Bardeesy
http://cancerdiscovery.aacrjournals.org/content/5/12/1247.abstract?etoc

Revisiting vitamin C and cancer
Colleen R. Reczek and Navdeep S. Chandel
http://www.sciencemag.org/content/350/6266/1317.full

Seeing mTORC1 specificity
Gwen R. Buel and John Blenis
http://www.sciencemag.org/content/351/6268/25.full

Glycolysis and EZH2 boost T cell weaponry against tumors
Glenn R Bantug and Christoph Hess
http://www.nature.com/ni/journal/v17/n1/full/ni.3346.html

NRF2 Drives Serine/Glycine Biosynthesis to Promote NSCLC Tumorigenesis
http://cancerdiscovery.aacrjournals.org/content/5/12/OF17.abstract?etoc

Defining how amino acid deprivation inhibits mTORC1
http://stke.sciencemag.org/content/8/405/ec357.abstract

Cachexia: The last illness
http://www.nature.com/news/cachexia-the-last-illness-1.18961

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