Metabolist – December 2013

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Cancer metabolism
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p53 status determines the role of autophagy in pancreatic tumour development
Mathias T. Rosenfeldt, Jim O’Prey, Jennifer P. Morton, Colin Nixon, Gillian MacKay, Agata Mrowinska, Amy Au, Taranjit Singh Rai, Liang Zheng, Rachel Ridgway, Peter D. Adams, Kurt I. Anderson, Eyal Gottlieb, Owen J. Sansom & Kevin M. Ryan
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12865.html

Tumour-associated mutant p53 drives the Warburg effect
Cen Zhang, Juan Liu, Yingjian Liang, Rui Wu, Yuhan Zhao, Xuehui Hong, Meihua Lin, Haiyang Yu, Lianxin Liu, Arnold J. Levine, Wenwei Hu and Zhaohui Feng
http://www.nature.com/ncomms/2013/131217/ncomms3935/full/ncomms3935.html

Glutamine-driven oxidative phosphorylation is a major ATP source in transformed mammalian cells in both normoxia and hypoxia.
Fan J, Kamphorst JJ, Mathew R, Chung MK, White E, Shlomi T, Rabinowitz JD.
http://www.nature.com/msb/journal/v9/n1/full/msb201365.html

The Histone H3 Methyltransferase G9A Epigenetically Activates the Serine-Glycine Synthesis Pathway to Sustain Cancer Cell Survival and Proliferation
Jane Ding, Tai Li, Xiangwei Wang, Erhu Zhao, Jeong-Hyeon Choi, Liqun Yang, Yunhong Zha, Zheng Dong, Shuang Huang, John M. Asara, Hongjuan Cui, Han-Fei Ding
http://www.cell.com/cell-metabolism/abstract/S1550-4131(13)00453-1

A New Specific Succinate-Glutamate Metabolomic Hallmark in Sdhx-Related Paragangliomas
Alessio Imperiale, François-Marie Moussallieh, Frédéric Sebag, Laurent Brunaud, Anne Barlier, Karim Elbayed, Philippe Bachellier, Bernard Goichot, Karel Pacak, Izzie-Jacques Namer, David Taïeb
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080539

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Metabolic inhibitors
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Targeting cisplatin-resistant human tumor cells with metabolic inhibitors.
Sullivan EJ, Kurtoglu M, Brenneman R, Liu H, Lampidis TJ.
http://link.springer.com/article/10.1007%2Fs00280-013-2366-8

Carbon Monoxide Expedites Metabolic Exhaustion to Inhibit Tumor Growth
Barbara Wegiel, David Gallo, Eva Csizmadia, Clair Harris, John Belcher, Gregory M. Vercellotti, Nuno Penacho, Pankaj Seth, Vikas Sukhatme, Asif Ahmed, Pier Paolo Pandolfi, Leszek Helczynski, Anders Bjartell, Jenny Liao Persson, and Leo E. Otterbein
http://cancerres.aacrjournals.org/content/73/23/7009.abstract.html?etoc

Inhibition of glycolysis attenuates 4-hydroxynonenal-dependent autophagy and exacerbates apoptosis in differentiated SH-SY5Y neuroblastoma cells
http://dx.doi.org/10.4161/auto.26094

Inhibition of Lipolysis by Mercaptoacetate and Etomoxir Specifically Sensitize Drug-Resistant Lung Adenocarcinoma Cell to Paclitaxel
Li, Jiajin; Zhao, Shiyan; Zhou, Xiang; Zhang, Teng; Zhao, Li; Miao, Ping; Song, Shaoli; Sun, Xiaoguang; Liu, Jianjun; Zhao, Xiaoping; Huang, Gang
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0074623

Arginine deiminase resistance in melanoma cells is associated with metabolic reprogramming, glucose dependence, and glutamine addiction.
Long Y, Tsai WB, Wangpaichitr M, Tsukamoto T, Savaraj N, Feun LG, Kuo MT.
http://mct.aacrjournals.org/content/12/11/2581.long

Glucose promotes breast cancer aggression and reduces metformin efficacy
Reema Wahdan-Alaswad, Zeying Fan, Susan M Edgerton, Bolin Liu, Xin-Sheng Deng, Sigrid Salling Arnadottir, Jennifer K Richer, Steven M Anderson and Ann D Thor
http://dx.doi.org/10.4161/cc.26641

Combined Targeting of PDK1 and EGFR Triggers Regression of Glioblastoma by Reversing the Warburg Effect
Kiran Kumar Velpula, Arnima Bhasin, Swapna Asuthkar, and  Andrew J. Tsung
http://cancerres.aacrjournals.org/content/73/24/7277.abstract.html?etoc

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Starvation / ischemia
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Increased sensitivity to glucose starvation correlates with downregulation of glycogen phosphorylase isoform PYGB in tumor cell lines resistant to 2-deoxy-D-glucose.
hilips KB, Kurtoglu M, Leung HJ, Liu H, Gao N, Lehrman MA, Murray TG, Lampidis TJ.
http://link.springer.com/article/10.1007%2Fs00280-013-2358-8

Metabolic regulation of cancer cell side population by glucose through activation of the Akt pathway
P-P Liu, J Liao, Z-J Tang, W-J Wu, J Yang, Z-L Zeng, Y Hu, P Wang, H-Q Ju, R-H Xu and P Huang
http://www.nature.com/cdd/journal/v21/n1/abs/cdd2013131a.html

Akt isoforms differentially protect against stroke-induced neuronal injury by regulating mTOR activities
Rong Xie, Michelle Cheng, Mei Li, Xiaoxing Xiong, Marcel Daadi, Robert M Sapolsky and Heng Zhao
http://www.nature.com/jcbfm/journal/v33/n12/abs/jcbfm2013132a.html

Autosis is a Na+,K+-ATPase–regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia–ischemia
Yang Liu, Sanae Shoji-Kawata, Rhea M. Sumpter, Jr., Yongjie Wei, Vanessa Ginet, Liying Zhang, Bruce Posner, Khoa A. Tran, Douglas R. Green, Ramnik J. Xavier, Stanley Y. Shaw, Peter G. H. Clarke, Julien Puyal, and Beth Levine
http://www.pnas.org/content/110/51/20364.abstract.html?etoc

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Hypoxia
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Impeding Macrophage Entry into Hypoxic Tumor Areas by Sema3A/Nrp1 Signaling Blockade Inhibits Angiogenesis and Restores Antitumor Immunity
Andrea Casazza, Damya Laoui, Mathias Wenes, Sabrina Rizzolio, Nicklas Bassani, Marco Mambretti, Sofie Deschoemaeker, Jo A. Van Ginderachter, Luca Tamagnone, Massimiliano Mazzone
http://www.cell.com/cancer-cell/abstract/S1535-6108(13)00494-7

CDK1 stabilizes HIF-1α via direct phosphorylation of Ser668 to promote tumor growth
Noel A Warfel, Nathan G Dolloff, David T Dicker, Jozef Malysz and Wafik S El-Deiry
http://dx.doi.org/10.4161/cc.26930

Peroxiredoxin-5 targeted to the mitochondrial intermembrane space attenuates hypoxia-induced reactive oxygen species signalling
Simran S. Sabharwal, Gregory B. Waypa, Jeremy D. Marks and Paul T. Schumacker
http://www.biochemj.org/bj/456/bj4560337.htm

ER stress and hypoxia response pathways interact to potentiate HIF-1 transcriptional activity on targets like VEGF
Ethel R. Pereira, Karen Frudd, Walid Awad, and Linda M. Hendershot
http://www.jbc.org/content/early/2013/12/17/jbc.M113.507194.abstract

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mTOR
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Regulation of PIK3C3/VPS34 complexes by MTOR in nutrient stress-induced autophagy
Hai-Xin Yuan, Ryan C Russell and Kun-Liang Guan
http://dx.doi.org/10.4161/auto.26058

Amino acids activate mTOR complex1 without changing Rag GTPase guanyl nucleotide charging
Noriko Oshiro, Joseph Rapley, and Joseph Avruch
http://www.jbc.org/content/early/2013/12/11/jbc.M113.528505.abstract

Crosstalk between the Tor and Gcn2 pathways in response to different stresses
[yeast]
Gro Elise Rødland, Tonje Tvegård, Erik Boye and Beáta Grallert
https://www.landesbioscience.com/journals/cc/article/27270/

p53/TAp63 and AKT Regulate mTORC1 Signaling through two Independent Parallel Pathways in the Presence of DNA Damage
Maren Cam, Hemant K. Bid, Linlin Xiao, Gerard P. Zambetti, Peter J. Houghton, and Hakan Cam
http://www.jbc.org/content/early/2013/12/23/jbc.M113.530303.abstract

Chemical Genetics of Rapamycin-Insensitive TORC2 in S. cerevisiae
[pentose phosphate pathway]
Joseph I. Kliegman, Dorothea Fiedler, Colm J. Ryan, Yi-Fan Xu, Xiao-yang Su, David Thomas, Max C. Caccese, Ada Cheng, Michael Shales, Joshua D. Rabinowitz, Nevan J. Krogan, Kevan M. Shokat
http://www.cell.com/cell-reports/abstract/S2211-1247(13)00724-9

T Cell Exit from Quiescence and Differentiation into Th2 Cells Depend on Raptor-mTORC1-Mediated Metabolic Reprogramming
Kai Yang, Sharad Shrestha, Hu Zeng, Peer W.F. Karmaus, Geoffrey Neale, Peter Vogel, David A. Guertin, Richard F. Lamb, Hongbo Chi
http://www.cell.com/immunity/abstract/S1074-7613(13)00506-2

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AMPK
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AMP-Activated Protein Kinase Induces p53 by Phosphorylating MDMX and Inhibiting Its Activity
Guifen He, Yi-Wei Zhang, Jun-Ho Lee, Shelya X. Zeng, Yunyuan V. Wang, Zhijun Luo, X. Charlie Dong, Benoit Viollet, Geoffrey M. Wahl, and Hua Lu
http://mcb.asm.org/cgi/content/abstract/34/2/148?etoc

Implication of transcriptional repression in compound C-induced apoptosis in cancer cells
Dai, RY; Zhao, XF; Li, JJ; Chen, R; Luo, ZL; Yu, LX; Chen, SK; Zhang,
CY; Duan, CY; Liu, YP; Feng, CH; Xia, XM; Li, H; Fu, J; Wang, HY
http://www.nature.com/cddis/journal/v4/n10/full/cddis2013419a.html

Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin
Morgan D Fullerton, Sandra Galic, Katarina Marcinko, Sarah Sikkema, Thomas Pulinilkunnil, Zhi-Ping Chen, Hayley M O’Neill, Rebecca J Ford, Rengasamy Palanivel, Matthew O’Brien, D Grahame Hardie, S Lance Macaulay, Jonathan D Schertzer, Jason R B Dyck, Bryce J van Denderen, Bruce E Kemp & Gregory R Steinberg
http://www.nature.com/nm/journal/v19/n12/full/nm.3372.html

Structural basis of AMPK regulation by small molecule activators
Bing Xiao, Matthew J. Sanders, David Carmena, Nicola J. Bright, Lesley F. Haire, Elizabeth Underwood, Bhakti R. Patel, Richard B. Heath, Philip A. Walker, Stefan Hallen, Fabrizio Giordanetto, Stephen R. Martin, David Carling and Steven J. Gamblin
http://www.nature.com/ncomms/2013/131219/ncomms4017/full/ncomms4017.html

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Miscellaneous
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Glyceraldehyde-3-phosphate Dehydrogenase Is Activated by Lysine 254 Acetylation in Response to Glucose Signal
Tingting Li, Mengxi Liu, Xu Feng, Zhen Wang, Indrani Das, Yanping Xu, Xin Zhou, Yiping Sun, Kun-Liang Guan, Yue Xiong, and Qun-Ying Lei
http://www.jbc.org/content/early/2013/12/21/jbc.M113.531640.abstract

Controllability in Cancer Metabolic Networks According to Drug Targets as Driver Nodes
Yazdan Asgari, Ali Salehzadeh-Yazdi, Falk Schreiber, Ali Masoudi-Nejad
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079397

Non-invasive in-cell determination of free cytosolic [NAD+]/[NADH] ratios using hyperpolarized glucose show large variations in metabolic phenotypes
Caspar Elo Christensen, Magnus Karlsson, Jakob R. Winther, Pernille Rose Jensen, and Mathilde H. Lerche
http://www.jbc.org/content/early/2013/12/03/jbc.M113.498626.abstract

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Correspondence
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2-Hydroxyglutarate is not a metabolite; d-2-hydroxyglutarate and l-2-hydroxyglutarate are!
Eduard A. Struys
http://www.pnas.org/content/110/51/E4939.extract.html?etoc

Reply to Struys: Role of biomarker of 2-hydroxyglutarate in acute myeloid leukemia
Yang Shen, Jing-Han Wang, Wen-Lian Chen, Wei Jia, Sai-Juan Chen, and Zhu Chen
http://www.pnas.org/content/110/51/E4940.extract.html?etoc

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Reviews
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Autophagy-Mediated Tumor Promotion
Jessie Yanxiang Guo, Bing Xia, Eileen White
http://www.cell.com/abstract/S0092-8674(13)01468-2

Hypoxia and metabolism in cancer.
Karim Bensaad, Adrian L. Harris
http://link.springer.com/chapter/10.1007%2F978-1-4614-5915-6_1

How does the metabolism of tumour cells differ from that of normal cells?
Nívea Dias Amoêdo, Juan Perez Valencia, Mariana Figueiredo Rodrigues, Antonio Galina and Franklin David Rumjanek
http://www.bioscirep.org/bsr/033/e080/bsr033e080.htm

Unfolded Protein Response Signaling and Metabolic Diseases
Jaemin Lee and Umut Ozcan
http://www.jbc.org/content/early/2013/12/09/jbc.R113.534743.abstract

Targeting Breast Cancer Metabolism: A Metabolic Control Analysis Approach
Ettore Murabito
http://www.omicsonline.org/targeting-breast-cancer-metabolism-a-metabolic-control-analysis-approach-2332-0737.1000104.php?aid=17033

Mitochondrial Dysfunction in Cancer
Michelle L Boland, Aparajita H Chourasia, and Kay F Macleod
http://www.frontiersin.org/Journal/10.3389/fonc.2013.00292/full

Lactate Dehydrogenase A in Cancer: A Promising Target for Diagnosis and Therapy
Miao, Ping; Sheng, Shile; Sun, Xiaoguang; Liu, Jianjun; Huang, Gang
http://onlinelibrary.wiley.com/doi/10.1002/iub.1216/abstract

Single-Cell Metabolomics: Analytical and Biological Perspectives
R. Zenobi
http://www.sciencemag.org/content/342/6163/1243259.abstract

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Comments
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Metformin trims fats to restore insulin sensitivity
Reuben J Shaw
http://www.nature.com/nm/journal/v19/n12/full/nm.3414.html

A critical role of glucose-6-phosphate dehydrogenase in TAp73-mediated cell proliferation
Peng Jiang, Wenjing Du and Xiaolu Yang
http://dx.doi.org/10.4161/cc.27267

Incomplete and transitory decrease of glycolysis: A new paradigm for anti-angiogenic therapy?
Sandra Schoors, Anna Rita Cantelmo, Maria Georgiadou, Peter Stapor, Xingwu Wang, Annelies Quaegebeur, Sandra Cauwenberghs, Brian W Wong, Francesco Bifari, Ilaria Decimo, Luc Schoonjans, Katrien De Bock, Mieke Dewerchin and Peter Carmeliet
https://www.landesbioscience.com/journals/cc/article/27519/

Mitochondrial metabolism in TCA cycle mutant cancer cells
Lucas B Sullivan and Navdeep S Chandel
https://www.landesbioscience.com/journals/cc/article/27513/

Cholesterol and Cancer
http://stke.sciencemag.org/cgi/content/abstract/sigtrans;6/304/ec292

K433 Acetylation Switches PKM2 to a Nuclear Kinase
http://cancerdiscovery.aacrjournals.org/content/3/12/1325.2.abstract.html?etoc

Regulation of PKM2 Activity Enables Metabolic Adaptation in Tumors
http://cancerdiscovery.aacrjournals.org/content/3/12/OF18.abstract.html?etoc

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