MetaboList – April 2019


Resources


Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability – Mark R Sullivan, Laura V Danai, Caroline A Lewis, Sze Ham Chan, Dan Y Gui, Tenzin Kunchok, Emily A Dennstedt, Matthew G Vander Heiden, Alexander Muir. https://elifesciences.org/articles/44235

Metabolic profiling of cancer cells reveals genome-wide crosstalk between transcriptional regulators and metabolism – Karin Ortmayr, Sébastien Dubuis and Mattia Zampieri. https://www.nature.com/articles/s41467-019-09695-9


Amino acid metabolism


Synthetic Lethality of Wnt Pathway Activation and Asparaginase in Drug-Resistant Acute Leukemias – Laura Hinze, Maren Pfirrmann, Salmaan Karim, James Degar, Connor McGuckin, Divya Vinjamur, Joshua Sacher, Kristen E. Stevenson, Donna S. Neuberg, Esteban Orellana, Martin Stanulla, Richard I. Gregory, Daniel E. Bauer, Florence F. Wagner, Kimberly Stegmaier, Alejandro Gutierrez. https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30149-7

Nutrient Stress–Dysregulated Antisense lncRNA GLS-AS Impairs GLS-Mediated Metabolism and Represses Pancreatic Cancer Progression – Shi-Jiang Deng, Heng-Yu Chen, Zhu Zeng, Shichang Deng, Shuai Zhu, Zeng Ye, Chi He, Ming-Liang Liu, Kang Huang, Jian-Xin Zhong, Feng-Yu Xu, Qiang Li, Yang Liu, Chunyou Wang and Gang Zhao. http://cancerres.aacrjournals.org/content/79/7/1398

Epigenetic Silencing Affects l-Asparaginase Sensitivity and Predicts Outcome in T-ALL – Aurore Touzart, Etienne Lengliné, Mehdi Latiri, Mohamed Belhocine, Charlotte Smith, Xavier Thomas, Salvatore Spicuglia, Denis Puthier, Françoise Pflumio, Thibaut Leguay, Carlos Graux, Yves Chalandon, Françoise Huguet, Stéphane Leprêtre, Norbert Ifrah, Hervé Dombret, Elizabeth Macintyre, Mathilde Hunault, Nicolas Boissel and Vahid Asnafi. http://clincancerres.aacrjournals.org/content/25/8/2483

Concurrent Targeting of Glutaminolysis and Metabotropic Glutamate Receptor 1 (GRM1) Reduces Glutamate Bioavailability in GRM1+ Melanoma – Raj Shah, Simar J. Singh, Kevinn Eddy, Fabian V. Filipp and Suzie Chen. http://cancerres.aacrjournals.org/content/79/8/1799

The Deubiquitylase OTUB1 Mediates Ferroptosis via Stabilization of SLC7A11 – Tong Liu, Le Jiang, Omid Tavana and Wei Gu. http://cancerres.aacrjournals.org/content/79/8/1913

Structure of the human LAT1–4F2hc heteromeric amino acid transporter complex – Renhong Yan, Xin Zhao, Jianlin Lei and Qiang Zhou. https://www.nature.com/articles/s41586-019-1011-z

Uncovering the Role of N-Acetyl-Aspartyl-Glutamate as a Glutamate Reservoir in Cancer – Tu Nguyen, Brian James Kirsch, Ryoichi Asaka, Karim Nabi, Addison Quinones, Jessica Tan, Marjorie Justine Antonio, Felipe Camelo, Ting Li, Stephanie Nguyen, Giang Hoang, Kiet Nguyen, Sunag Udupa, Christos Sazeides, Yao-An Shen, Amira Elgogary, Juvenal Reyes, Liang Zhao, Andre Kleensang, Kaisorn Lee Chaichana, Thomas Hartung, Michael J. Betenbaugh, Suely K. Marie, Jin G. Jung, Tian-Li Wang, Edward Gabrielson, Anne Le. https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30352-3

LLGL2 rescues nutrient stress by promoting leucine uptake in ER+ breast cancer – Yasuhiro Saito, Lewyn Li, Etienne Coyaud, Augustin Luna, Chris Sander, Brian Raught, John M. Asara, Myles Brown and Senthil K. Muthuswamy. https://www.nature.com/articles/s41586-019-1126-2


Lipid and acetyl-CoA metabolism


An allosteric mechanism for potent inhibition of human ATP-citrate lyase – Jia Wei, Silvana Leit, Jun Kuai et al. https://www.nature.com/articles/s41586-019-1094-6

Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle – Koen H. G. Verschueren, Clement Blanchet, Jan Felix et al. https://www.nature.com/articles/s41586-019-1095-5

Statin-dependent modulation of mitochondrial metabolism in cancer cells is independent of cholesterol content – Charleston F. Christie, Diana Fang, Elizabeth G. Hunt, Morgan E. Morris, Amandine Rovini, Kareem A. Heslop, Gyda C. Beeson, Craig C. Beeson and Eduardo N. Maldonado. https://www.fasebj.org/doi/abs/10.1096/fj.201802723R?ai=ts&ui=ly8&af=T

ACOT12-Dependent Alteration of Acetyl-CoA Drives Hepatocellular Carcinoma Metastasis by Epigenetic Induction of Epithelial-Mesenchymal Transition – Ming Lu, Wen-Wei Zhu, Xuan Wang, Jing-Jie Tang, Kai-Li Zhang, Guang-Yang Yu, Wei-Qing Shao, Zhi-Fei Lin, Sheng-Hao Wang, Lu Lu, Jian Zhou, Lian-Xin Wang, Hu-Liang Jia, Qiong-Zhu Dong, Jin-Hong Chen, Jian-Quan Lu, Lun-Xiu Qin. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30756-3


Nucleotides and NAD


NAD metabolic dependency in cancer is shaped by gene amplification and enhancer remodelling – Sudhir Chowdhry, Ciro Zanca, Utkrisht Rajkumar, Tomoyuki Koga, Yarui Diao, Ramya Raviram, Feng Liu, Kristen Turner, Huijun Yang, Elizabeth Brunk, Junfeng Bi, Frank Furnari, Vineet Bafna, Bing Ren and Paul S. Mischel. https://www.nature.com/articles/s41586-019-1150-2

Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion – Irmina A. Elliott, Amanda M. Dann, Shili Xu, Stephanie S. Kim, Evan R. Abt, Woosuk Kim, Soumya Poddar, Alexandra Moore, Lei Zhou, Jennifer L. Williams, Joseph R. Capri, Razmik Ghukasyan, Cynthia Matsumura, D. Andrew Tucker, Wesley R. Armstrong, Anthony E. Cabebe, Nanping Wu, Luyi Li, Thuc M. Le, Caius G. Radu and Timothy R. Donahue. https://www.pnas.org/content/116/14/6842.abstract?etoc

Cancer stem-like properties and gefitinib resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2 – Tatsunori Nishimura, Asuka Nakata, Xiaoxi Chen, Kurumi Nishi, Makiko Meguro-Horike, Soichiro Sasaki, Kenji Kita, Shin-ichi Horike, Kaori Saitoh, Keiko Kato, Kaori Igarashi, Takahiko Murayama, Susumu Kohno, Chiaki Takahashi, Naofumi Mukaida, Seiji Yano, Tomoyoshi Soga, Arinobu Tojo and Noriko Gotoh. https://www.nature.com/articles/s41388-018-0589-1


Mitochondria


ER and Nutrient Stress Promote Assembly of Respiratory Chain Supercomplexes through the PERK-eIF2α Axis – Eduardo Balsa, Meghan S.Soustek, Ajith Thomas, Sara Cogliati, Carolina García-Poyatos, Elena Martín-García, Mark Jedrychowski, Steve P. Gygi, José Antonio Enriquez, Pere Puigserver. https://www.sciencedirect.com/science/article/pii/S1097276519302357

Cytochrome c Deficiency Confers Apoptosome and Mitochondrial Dysfunction in African-American Men with Prostate Cancer – Rahul Kumar, Tariq A. Bhat, Elise M. Walsh, Ajay K. Chaudhary, Jordan O’Malley, Johng S. Rhim, Jianmin Wang, Carl D. Morrison, Kristopher Attwood, Wiam Bshara, James L. Mohler, Neelu Yadav and Dhyan Chandra. http://cancerres.aacrjournals.org/content/79/7/1353

Retrodifferentiation of Human Tumor Hepatocytes to Stem Cells Leads to Metabolic Reprogramming and Chemoresistance – Karim Fekir, Hélène Dubois-Pot-Schneider, Romain Désert, Yoann Daniel, Denise Glaise, Claudine Rauch, Fabrice Morel, Bernard Fromenty, Orlando Musso, Florian Cabillic and Anne Corlu. http://cancerres.aacrjournals.org/content/79/8/1869

Lethal Poisoning of Cancer Cells by Respiratory Chain Inhibition plus Dimethyl α-Ketoglutarate – Valentina Sica, Jose Manuel Bravo-San Pedro, Valentina Izzo, Jonathan Pol, Sandra Pierredon, David Enot, Sylvère Durand, Noélie Bossut, Alexis Chery, Sylvie Souquere, Gerard Pierron, Evangelia Vartholomaiou, Naoufal Zamzami, Thierry Soussi, Allan Sauvat, Laura Mondragón, Oliver Kepp, Lorenzo Galluzzi, Jean-Claude Martinou, Holger Hess-Stumpp, Karl Ziegelbauer, Guido Kroemer, Maria Chiara Maiuri. https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30388-2

Mitochondrial metabolism is inhibited by the HIF1α‐MYC‐PGC‐1β axis in BRAF V600E thyroid cancer – Yanyan Gao, Fang Yang, Xiu‐An Yang, Li Zhang,Huixin Yu, Xian Cheng, Shichen Xu, Jie Pan, Kun Wang, Peifeng Li. https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.14786

Lactic acidosis due to repressed lactate dehydrogenase subunit B expression down-regulates mitochondrial oxidative phosphorylation via the PDK/PDH axis – Sun Mi Hong, Young-Kyoung Lee, Imkyong Park, So Mee Kwon, Seongki Min and Gyesoon Yoon. http://www.jbc.org/content/early/2019/03/28/jbc.RA118.006095.abstract

TIGAR regulates mitochondrial functions through SIRT1-PGC1α pathway and translocation of TIGAR into mitochondria in skeletal muscle – Ji Geng, Mingzhen Wei, Xiao Yuan, Ziqi Liu, Xinxin Wang, Dingmei Zhang, Li Luo, Junchao Wu, Wenjie Guo and Zheng-Hong Qin. https://www.fasebj.org/doi/abs/10.1096/fj.201802209R?ai=s4&ui=ly8&af=T


Starvation / Nutrient sensing


Intrinsic Structural Features of the Human IRE1α Transmembrane Domain Sense Membrane Lipid Saturation– Hyunju Cho, Francesca Stanzione, Amrita Oak, Geun Hyang Kim, Sindura Yerneni, Ling Qi, Amadeu K. Sum, Christina Chan. https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30324-9

The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation – Katarzyna Parzych, Paula Saavedra-García, Gabriel N. Valbuena, Hibah A. Al-Sadah, Mark E. Robinson, Lucy Penfold, Desislava M. Kuzeva, Angie Ruiz-Tellez, Sandra Loaiza, Viktoria Holzmann, Valentina Caputo, David C. Johnson, Martin F. Kaiser, Anastasios Karadimitris, Eric W-F Lam, Eric Chevet, Niklas Feldhahn, Hector C. Keun and Holger W. Auner. https://www.nature.com/articles/s41388-018-0651-z

Probing the Global Cellular Responses to Lipotoxicity Caused by Saturated Fatty Acids – Manuele Piccolis, Laura M. Bond, Martin Kampmann, Pamela Pulimeno, Chandramohan Chitraju, Christina B.K. Jayson, Laura P. Vaites, Sebastian Boland, Zon Weng Lai, Katlyn R. Gabriel, Shane D. Elliott, Joao A. Paulo, J. Wade Harper, Jonathan S. Weissman, Tobias C. Walther, Robert V. Farese Jr. https://www.cell.com/molecular-cell/fulltext/S1097-2765(19)30056-5

Eukaryotic elongation factor 2 (eEF2) kinase/eEF2 plays protective roles against glucose deprivation-induced cell death in H9c2 cardiomyoblasts – Satoshi Kameshima, Muneyoshi Okada and Hideyuki Yamawaki. https://link.springer.com/article/10.1007/s10495-019-01525-z


mTOR / AMPK


Phenformin, But Not Metformin, Delays Development of T Cell Acute Lymphoblastic Leukemia/Lymphoma via Cell-Autonomous AMPK Activation – Diana Vara-Ciruelos, Madhumita Dandapani, Fiona M. Russell, Katarzyna M. Grzes, Abdelmadjid Atrih, Marc Foretz, Benoit Viollet, Douglas J. Lamont, Doreen A. Cantrell, D. Grahame Hardie. https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30397-3

Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling – Gabriella M. Forte, Elizabeth Davie, Shervi Lie, Mirita Franz-Wachtel,Ashley J. Ovens, Tingting Wang, Jonathan S. Oakhill, Boris Maček, Iain M.Hagan and Janni Petersen. http://jcs.biologists.org/content/132/7/jcs223925?etoc

Yeast Ataxin-2 Forms an Intracellular Condensate Required for the Inhibition of TORC1 Signaling during Respiratory Growth – Yu-San Yang, Masato Kato, Xi Wu, Athanasios Litsios, Benjamin M. Sutter, Yun Wang, Chien-Hsiang Hsu, N. Ezgi Wood, Andrew Lemoff, Hamid Mirzaei, Matthias Heinemann, Benjamin P. Tu. https://www.cell.com/cell/fulltext/S0092-8674(19)30226-0

TORC1 modulation in adipose tissue is required for organismal adaptation to hypoxia in Drosophila – Byoungchun Lee, Elizabeth C. Barretto and Savraj S. Grewal. https://www.nature.com/articles/s41467-019-09643-7


Hypoxia


Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy – Youqiong Ye, Qingsong Hu, Hu Chen, Ke Liang, Yuan Yuan, Yu Xiang, Hang Ruan, Zhao Zhang, Anren Song, Huiwen Zhang, Lingxiang Liu, Lixia Diao, Yanyan Lou, Bingying Zhou, Li Wang, Shengtao Zhou, Jianjun Gao, Eric Jonasch, Steven H. Lin, Yang Xia, Chunru Lin, Liuqing Yang, Gordon B. Mills, Han Liang and Leng Han. https://www.nature.com/articles/s42255-019-0045-8

A Feedback Loop between Hypoxia and Matrix Stress Relaxation Increases Oxygen-Axis Migration and Metastasis in Sarcoma – Daniel M. Lewis, Hawley Pruitt, Nupur Jain, Mark Ciccaglione, J. Michael McCaffery, Zhiyong Xia, Kristy Weber, T.S. Karin Eisinger-Mathason and Sharon Gerecht. http://cancerres.aacrjournals.org/content/79/8/1981


Cancer immunometabolism


Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells – Fei Chen, Jianing Chen, Linbin Yang, Jiang Liu, Xiaoqian Zhang, Yin Zhang, Qingqiang Tu, Dong Yin, Dechen Lin, Ping-Pui Wong, Di Huang, Yue Xing, Jinghua Zhao, Mengfeng Li, Qiang Liu, Fengxi Su, Shicheng Su and Erwei Song. https://www.nature.com/articles/s41556-019-0299-0

HIF-1α Is a Metabolic Switch between Glycolytic-Driven Migration and Oxidative Phosphorylation-Driven Immunosuppression of Tregs in Glioblastoma – Jason Miska, Catalina Lee-Chang, Aida Rashidi, Megan E. Muroski, Alan L. Chang, Aurora Lopez-Rosas, Peng Zhang, Wojciech K. Panek, Alex Cordero, Yu Han, Atique U. Ahmed, Navdeep S. Chandel, Maciej S. Lesniak. https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30345-6

Microenvironmental oxygen pressure orchestrates an anti- and pro-tumoral γδ T cell equilibrium via tumor-derived exosomes – Ling Li, Bangrong Cao, Xinhua Liang, Shun Lu, Huaichao Luo, Zhaohui Wang, Shaoxin Wang, Jian Jiang, Jinyi Lang and Guiquan Zhu. https://www.nature.com/articles/s41388-018-0627-z

Fatty acid transport protein 2 reprograms neutrophils in cancer – Filippo Veglia, Vladimir A. Tyurin, Maria Blasi, Alessandra De Leo, Andrew V. Kossenkov, Laxminarasimha Donthireddy, Tsun Ki Jerrick To, Zach Schug, Subhasree Basu, Fang Wang, Emanuela Ricciotti, Concetta DiRusso, Maureen E. Murphy, Robert H. Vonderheide, Paul M. Lieberman, Charles Mulligan, Brian Nam, Neil Hockstein, Gregory Masters, Michael Guarino, Cindy Lin, Yulia Nefedova, Paul Black, Valerian E. Kagan and Dmitry I. Gabrilovich. https://www.nature.com/articles/s41586-019-1118-2


Miscellaneous


Stratification of cancer and diabetes based on circulating levels of formate and glucose – Matthias Pietzke, Salvador Fernandez Arroyo, David Sumpton, Gillian M. Mackay, Begoña Martin-Castillo, Jordi Camps, Jorge Joven, Javier A. Menendez and Alexei Vazquez. https://cancerandmetabolism.biomedcentral.com/

The adverse effect of gentamicin on cell metabolism in three cultured mammary cell lines: “Are cell culture data skewed?” – Robert L. Elliott, Xian-Peng Jiang. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214586


Reviews


Energy metabolism in cachexia – Maria Rohm, Anja Zeigerer, Juliano Machado and Stephan Herzig. http://EMBOr.embopress.org/content/20/4/e47258?etoc

Watch What You (Self-) Eat: Autophagic Mechanisms that Modulate Metabolism – Vikramjit Lahiri, Wayne D. Hawkins, Daniel J. Klionsky. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30131-7

Targeting Metabolic–Redox Circuits for Cancer Therapy – Kui Wang, Jingwen Jiang, Yunlong Lei, Shengtao Zhou, Yuquan Wei, Canhua Huang. https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(19)30001-5

Metabolism-Based Therapeutic Strategies Targeting Cancer Stem Cells – Petra Jagust, Beatriz de Luxán-Delgado, Beatriz Parejo-Alonso and Patricia Sancho. https://www.frontiersin.org/articles/10.3389/fphar.2019.00203/full

Mitochondrial stress-dependent regulation of cellular protein synthesis – Ulrike Topf, Barbara Uszczynska-Ratajczak and Agnieszka Chacinska. http://jcs.biologists.org/content/132/8/jcs226258?etoc

Micromanaging aerobic respiration and glycolysis in cancer cells – Ayla V. Orang, Janni Petersen, Ross A. McKinnon, Michael Z. Michael. https://www.sciencedirect.com/science/article/pii/S2212877818311128

The mystery of metformin – Martin J. Spiering. http://www.jbc.org/content/294/17/6689.full.html


Comments


Several Faces of Glutaminase Regulation in Cells – Ana C.P. Mafra and Sandra M.G. Dias. http://cancerres.aacrjournals.org/content/79/7/1302

Metabolic Adaptation Fuels Lymph Node Metastasis – Jessalyn M. Ubellacker, Sean J. Morrison. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30134-2

Mechanical forces rewire metabolism in the tumor niche – Thomas Bertero and Cedric Gaggioli. https://www.tandfonline.com/doi/full/10.1080/23723556.2019.1592945

Uncovering Plasticity in Tumor Lipid Metabolism – http://cancerdiscovery.aacrjournals.org/content/9/4/456.2

Renovation in progress [pyruvate] – Ulrike Harjes. https://www.nature.com/articles/s41568-019-0131-y

Overflow [of glucose] disrupts the genome – Ulrike Harjes. https://www.nature.com/articles/s41568-019-0136-6

Targeting cancer cell metabolism in glioblastoma – Sarah Crunkhorn. https://www.nature.com/articles/s41568-019-0139-3

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