MetaboList – May 2021


Miscellaneous


Mammary epithelial cells have lineage-rooted metabolic identities – Mathepan Jeya Mahendralingam, Hyeyeon Kim, Curtis William McCloskey, Kazeera Aliar, Alison Elisabeth Casey, Pirashaanthy Tharmapalan, Davide Pellacani, Vladimir Ignatchenko, Mar Garcia-Valero, Luis Palomero, Ankit Sinha, Jennifer Cruickshank, Ronak Shetty, Ravi N. Vellanki, Marianne Koritzinsky, Vid Stambolic, Mina Alam, Aaron David Schimmer, Hal Kenneth Berman, Connie J. Eaves, Miquel Angel Pujana, Thomas Kislinger and Rama Khokha. https://www.nature.com/articles/s42255-021-00388-6

NOX4 links metabolic regulation in pancreatic cancer to endoplasmic reticulum redox vulnerability and dependence on PRDX4 – Pallavi Jain, Anna Dvorkin-Gheva, Erik Mollen, Lucie Malbeteau, Michael Xie, Fatima Jessa, Piriththiv  Dhavarasa, Stephen Chung, Kevin R. Brown, Gun Ho Jang, Parth Vora, Faiyaz Notta, Jason Moffat, David  Hedley, Paul C. Boutros, Bradly G. Wouters, Marianne Koritzinsky. https://advances.sciencemag.org/content/7/19/eabf7114

Pharmacological inhibition of PI5P4Kα/β disrupts cell energy metabolism and selectively kills p53-null tumor cells – Song Chen, Caroline Chandra Tjin, Xiang Gao, Yi Xue, Haoyan Jiao, Ruilin Zhang, Mengnan Wu, Zunyu He, Jonathan Ellman, and Ya Ha. https://www.pnas.org/content/118/21/e2002486118.abstract?etoc

Mitochondrial Inhibitor Atovaquone Increases Tumor Oxygenation and Inhibits Hypoxic Gene Expression in Patients with Non–Small Cell Lung Cancer – Michael Skwarski, Daniel R. McGowan, Elizabeth Belcher, Francesco Di Chiara, Dionisios Stavroulias, Mark McCole, Jennifer L. Derham, Kwun-Ye Chu, Eugene Teoh, Jagat Chauhan, Dawn O’Reilly, Benjamin H.L. Harris, Philip S. Macklin, Joshua A. Bull, Marcus Green, Gonzalo Rodriguez-Berriguete, Remko Prevo, Lisa K. Folkes, Leticia Campo, Petra Ferencz, Paula L. Croal, Helen Flight, Cathy Qi, Jane Holmes, James P.B. O’Connor, Fergus V. Gleeson, W. Gillies McKenna, Adrian L. Harris, Daniel Bulte, Francesca M. Buffa, Ruth E. Macpherson and Geoff S. Higgins. https://clincancerres.aacrjournals.org/content/27/9/2459

Phase I Assessment of Safety and Therapeutic Activity of BAY1436032 in Patients with IDH1-Mutant Solid Tumors – Antje Wick, Oliver Bähr, Martin Schuler, Kristoffer Rohrberg, Sant P. Chawla, Filip Janku, David Schiff, Volker Heinemann, Yoshitaka Narita, Heinz-Josef Lenz, Masafumi Ikeda, Yuichi Ando, Wolfgang Wick, Joachim P. Steinbach, Michael C. Burger, Katharina Wenger, Ulrik Lassen, Kamalesh K. Sankhala, Cristiana Roggia, Isabelle Genvresse, Catya Munhoz, Christine Rentzsch, Susanne Reschke, Simon Langer, Markus Wagner, Stefan Kaulfuss, Charles Cai, Eleni Lagkadinou, Michael Jeffers, Carol Peña and Ghazaleh Tabatabai. https://clincancerres.aacrjournals.org/content/27/10/2723


Amino acid metabolism


Downregulation of Glutamine Synthetase, not glutaminolysis, is responsible for glutamine addiction in Notch1‐driven acute lymphoblastic leukemia – Tra Ly Nguyen, Marie‐Julie Nokin, Silvia Terés, Mercedes Tomé, Clément Bodineau, Oriane Galmar, Jean‐Max Pasquet, Benoit Rousseau, Sebastian van Liempd, Juan Manuel Falcon‐Perez, Elodie Richard, Elodie Muzotte, Hamid‐Reza Rezvani, Muriel Priault, Marion Bouchecareilh, Isabelle Redonnet‐Vernhet, Julien Calvo, Benjamin Uzan, Françoise Pflumio, Patricia Fuentes, Maria L. Toribio, Abdel‐Majid Khatib, Pierre Soubeyran, Piedad del Socorro Murdoch, Raúl V. Durán. https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.12877

Glutaminolysis dynamics during astrocytoma progression correlates with tumor aggressiveness – Yollanda E. Moreira Franco, Maria Jose Alves, Miyuki Uno, Isabele Fattori Moretti, Marina Trombetta-Lima, Suzana de Siqueira Santos, Ancely Ferreira dos Santos, Gabriel Santos Arini, Mauricio S. Baptista, Antonio Marcondes Lerario, Sueli Mieko Oba-Shinjo and Suely Kazue Nagahashi Marie. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-021-00255-8

Exogenous and Endogenous Sources of Serine Contribute to Colon Cancer Metabolism, Growth, and Resistance to 5-Fluorouracil – David C. Montrose, Suchandrima Saha, Miguel Foronda, Erin M. McNally, Justin Chen, Xi Kathy Zhou, Taehoon Ha, Jan Krumsiek, Mustafa Buyukozkan, Akanksha Verma, Olivier Elemento, Rhonda K. Yantiss, Qiuying Chen, Steven S. Gross, Lorenzo Galluzzi, Lukas E. Dow and Andrew J. Dannenberg. https://cancerres.aacrjournals.org/content/81/9/2275


Lipid metabolism


Posttranscriptional regulation of de novo lipogenesis by glucose-induced O-GlcNAcylation – Wei Tan, Pei Jiang, Wanjun Zhang, Zhaohua Hu, Shaofeng Lin, Lulu Chen, Yingge Li, Changmin Peng, Zhuqing Li, Aihua Sun, Yali Chen, Wenge Zhu, Yu Xue, Yi Yao, Xiangpan Li, Qibin Song, Fuchu He, Weijie Qin, Huadong Pei. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00095-2

Mevalonate Pathway Inhibition Slows Breast Cancer Metastasis via Reduced N-glycosylation Abundance and Branching – Rosemary Yu, Joseph Longo, Jenna E. van Leeuwen, Cunjie Zhang, Emily Branchard, Mohamad Elbaz, David W. Cescon, Richard R. Drake, James W. Dennis and Linda Z. Penn. https://cancerres.aacrjournals.org/content/81/10/2625

HMGCR inhibition stabilizes the glycolytic enzyme PKM2 to support the growth of renal cell carcinoma – Jiajun Huang, Xiaoyu Zhao, Xiang Li, Jiwei Peng, Weihao Yang, Shengli Mi. https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001197


Nucleotides


DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer – Chao Mao, Xiaoguang Liu, Yilei Zhang, Guang Lei, Yuelong Yan, Hyemin Lee, Pranavi Koppula, Shiqi Wu, Li Zhuang, Bingliang Fang, Masha V. Poyurovsky, Kellen Olszewski and Boyi Gan. https://www.nature.com/articles/s41586-021-03539-7

IMPDH inhibitors for antitumor therapy in tuberous sclerosis complex – Alexander J Valvezan, Molly C McNamara, Spencer K Miller, Margaret E Torrence, John M Asara, Elizabeth P Henske, Brendan D Manning. https://insight.jci.org/articles/view/135071

Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity – Hans-Georg Sprenger, Thomas MacVicar, Amir Bahat, Kai Uwe Fiedler, Steffen Hermans, Denise Ehrentraut, Katharina Ried, Dusanka Milenkovic, Nina Bonekamp, Nils-Göran Larsson, Hendrik Nolte, Patrick Giavalisco and Thomas Langer. https://www.nature.com/articles/s42255-021-00385-9


Mitochondria


Loss of LUC7L2 and U1 snRNP subunits shifts energy metabolism from glycolysis to OXPHOS – Alexis A. Jourdain, Bridget E. Begg, Eran Mick, Hardik Shah, Sarah E. Calvo, Owen S. Skinner, Rohit Sharma, Steven M. Blue, Gene W. Yeo, Christopher B. Burge, Vamsi K. Mootha. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00143-X

Physiological concentrations of cyanide stimulate mitochondrial Complex IV and enhance cellular bioenergetics – Elisa B. Randi, Karim Zuhra, Laszlo Pecze, Theodora Panagaki, and Csaba Szabo. https://www.pnas.org/content/118/20/e2026245118.abstract?etoc

Inhibition of glycolysis and mitochondrial respiration promotes radiosensitisation of neuroblastoma and glioma cells – Donna L. Nile, Colin Rae, David J. Walker, Joe Canning Waddington, Isabel Vincent, Karl Burgess, Mark N. Gaze, Robert J. Mairs and Anthony J. Chalmers. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-021-00258-5

TNF-α differentially modulates subunit levels of respiratory electron transport complexes of ER/PR +ve/−ve breast cancer cells to regulate mitochondrial complex activity and tumorigenic potential – Anjali Shinde, Hyeryeon Jung, Hayun Lee, Kritarth Singh, Milton Roy, Dhruv Gohel, Han Byeol Kim, Minal Mane, Hitesh Vasiyani, Fatema Currim, Yu Ri Seo, Seojin Yang, Ara Cho, Eugene C. Yi and Rajesh Singh. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-021-00254-9

Malic enzyme 2 connects the Krebs cycle intermediate fumarate to mitochondrial biogenesis – Yi-Ping Wang, Azeem Sharda, Shuang-Nian Xu, Nick van Gastel, Cheuk Him Man, Una Choi, Wei Zhong Leong, Xi Li, David T. Scadden. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00110-8


Heme and iron


Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy – Cristian Sandoval-Acuña, Natalia Torrealba, Veronika Tomkova, Sukanya B. Jadhav, Kristyna Blazkova, Ladislav Merta, Sandra Lettlova, Miroslava K. Adamcová, Daniel Rosel, Jan Brábek, Jiri Neuzil, Jan Stursa, Lukas Werner and Jaroslav Truksa. https://cancerres.aacrjournals.org/content/81/9/2289

HIF-2α activation potentiates oxidative cell death in colorectal cancers by increasing cellular iron – Rashi Singhal, Sreedhar R. Mitta, Nupur K. Das, Samuel A. Kerk, Peter Sajjakulnukit, Sumeet Solanki, Anthony Andren, Roshan Kumar, Kenneth P. Olive, Ruma Banerjee, Costas A. Lyssiotis, Yatrik M. Shah. https://www.jci.org/articles/view/143691

Heme catabolism by tumor-associated macrophages controls metastasis formation – Francesca Maria Consonni, Augusto Bleve, Maria Grazia Totaro, Mariangela Storto, Paolo Kunderfranco, Alberto Termanini, Fabio Pasqualini, Chiara Alì, Chiara Pandolfo, Francesco Sgambelluri, Giulia Grazia, Mario Santinami, Andrea Maurichi, Massimo Milione, Marco Erreni, Andrea Doni, Marco Fabbri, Laura Gribaldo, Eliana Rulli, Miguel Parreira Soares, Valter Torri, Roberta Mortarini, Andrea Anichini and Antonio Sica. https://www.nature.com/articles/s41590-021-00921-5

BNIP3 promotes HIF‐1α‐driven melanoma growth by curbing intracellular iron homeostasis – Mónica Vara-Pérez, Matteo Rossi, Chris Van den Haute, Hannelore Maes, Maria Livia Sassano, Vivek Venkataramani, Bernhard Michalke, Erminia Romano, Kristine Rillaerts, Abhishek D Garg, Corentin Schepkens, Francesca M Bosisio, Jasper Wouters, Ana Isabel Oliveira, Peter Vangheluwe, Wim Annaert, Johannes V Swinnen, Jean Marie Colet, Joost J van den Oord, Sarah-Maria Fendt, Massimiliano Mazzone, Patrizia Agostinis. https://www.embopress.org/doi/full/10.15252/embj.2020106214


Glucose metabolism


Hexose-6-phosphate dehydrogenase blockade reverses prostate cancer drug resistance in xenograft models by glucocorticoid inactivation – Jianneng Li , Michael Berk, Mohammad Alyamani, Navin Sabharwal, Christopher Goins, Joseph Alvarado, Mehdi Baratchian, Ziqi Zhu, Shaun Stauffer, Eric A. Klein, Nima Sharifi. https://stm.sciencemag.org/content/13/595/eabe8226

MIG‐6 is essential for promoting glucose metabolic reprogramming and tumor growth in triple‐negative breast cancer – Jiabei He, Chien‐Feng Li, Hong‐Jen Lee, Dong‐Hui Shin, Yi‐Jye Chern, Bruno Pereira De Carvalho, Chia‐Hsin Chan. https://www.embopress.org/doi/full/10.15252/embr.202050781


Starvation / metabolic stress


Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR – Sophie Kaspar, Christian Oertlin, Karolina Szczepanowska, Alexandra Kukat, Katharina Senft, Christina Lucas, Susanne Brodesser, Maria Hatzoglou, Ola Larsson, Ivan Topisirovic, Aleksandra Trifunovic. https://advances.sciencemag.org/content/7/22/eabf0971

Cancer cells escape autophagy inhibition via NRF2-induced macropinocytosis – Hua Su, Fei Yang, Rao Fu, Xin Li, Randall French, Evangeline Mose, Xiaohong Pu, Brittney Trinh, Avi Kumar, Junlai Liu, Laura Antonucci, Jelena Todoric, Yuan Liu, Yinling Hu, Maria T. Diaz-Meco, Jorge Moscat, Christian M. Metallo, Andrew M. Lowy, Beicheng Sun, Michael Karin. https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00118-5

Bafilomycin A1 enhances NLRP3 inflammasome activation in human monocytes independent of lysosomal acidification – Shi Yu, Jack Green, Rose Wellens, Gloria Lopez‐Castejon, David Brough. https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15619

Glucose deprivation induced aberrant FUT1-mediated fucosylation drives cancer stemness in hepatocellular carcinoma – Jane H.C. Loong, Tin-Lok Wong, Man Tong, Rakesh Sharma, Lei Zhou, Kai-Yu Ng, Hua-Jian Yu, Chi Han Li, Kwan Man, Chung-Mau Lo, Xin-Yuan Guan, Terence K. Lee, Jing-Ping Yun, Stephanie Kwai Yee Ma. https://www.jci.org/articles/view/143377


mTOR


mTORC1 promotes cell growth via m6A-dependent mRNA degradation – Sungyun Cho, Gina Lee, Brian F. Pickering, Cholsoon Jang, Jin H. Park, Long He, Lavina Mathur, Seung-Soo Kim, Sunhee Jung, Hong-Wen Tang, Sebastien Monette, Joshua D. Rabinowitz, Norbert Perrimon, Samie R. Jaffrey, John Blenis. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00178-7

mTORC1 stimulates cell growth through SAM synthesis and m6A mRNA-dependent control of protein synthesis – Elodie Villa, Umakant Sahu, Brendan P. O’Hara, Eunus S. Ali, Kathryn A. Helmin, John M. Asara, Peng Gao, Benjamin D. Singer, Issam Ben-Sahra. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00177-5


Cancer Immunometabolism


CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability – Xingzhe Ma, Liuling Xiao, Lintao Liu, Lingqun Ye, Pan Su, Enguang Bi, Qiang Wang, Maojie Yang, Jianfei Qian, Qing Yi. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00071-1

Chromatin accessibility governs the differential response of cancer and T cells to arginine starvation – Nicholas T. Crump, Andreas V. Hadjinicolaou, Meng Xia, John Walsby-Tickle, Uzi Gileadi, Ji-Li Chen, Mashiko Setshedi, Lars R. Olsen, I-Jun Lau, Laura Godfrey, Lynn Quek, Zhanru Yu, Erica Ballabio, Mike B. Barnkob, Giorgio Napolitani, Mariolina Salio, Hashem Koohy, Benedikt M. Kessler, Stephen Taylor, Paresh Vyas, James S.O. McCullagh, Thomas A. Milne, Vincenzo Cerundolo. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00435-6

GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy – Pierre-Benoit Ancey, Caroline Contat, Gael Boivin, Silvia Sabatino, Justine Pascual, Nadine Zangger, Jean Yannis Perentes, Solange Peters, E. Dale Abel, David G. Kirsch, Jeffrey C. Rathmell, Marie-Catherine Vozenin and Etienne Meylan. https://cancerres.aacrjournals.org/content/81/9/2345


Methods


High-resolution spatiotemporal pHe and pO2 imaging in head and neck and oesophageal carcinoma cells – Alexandra Blancke Soares, Robert Meier, Gregor Liebsch, Sabina Schwenk-Zieger, Martin E. Kirmaier, Sebastian Theurich, Magdalena Widmann, Martin Canis, Olivier Gires and Frank Haubner. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-021-00257-6

Quantum monitoring of cellular metabolic activities in single mitochondria – Nie, A. C. Nusantara, V. G. Damle, R. Sharmin, E. P. P. Evans, S. R. Hemelaar, K. J. van der Laan, R. Li, F. P. Perona Martinez, T. Vedelaar, M. Chipaux, R. Schirhagl. https://advances.sciencemag.org/content/7/21/eabf0573


Reviews


Lipid metabolism in cancer: New perspectives and emerging mechanisms – Lindsay A. Broadfield, Antonino Alejandro Pane, Ali Talebi, Johannes V. Swinnen, Sarah-Maria Fendt. https://www.cell.com/developmental-cell/fulltext/S1534-5807(21)00322-1

Targeting nucleotide metabolism as the nexus of viral infections, cancer, and the immune response – Yarden Ariav, James H Ch’ng, Heather R. Christofk, Noga Ron-Harel, Ayelet Erez. https://advances.sciencemag.org/content/7/21/eabg6165

The functional roles of TCA cycle metabolites in cancer – Joseph Eniafe and Shuai Jiang. https://www.nature.com/articles/s41388-020-01639-8

Autophagy in metabolism and quality control: opposing, complementary or interlinked functions? – Vojo Deretic and Guido Kroemer. https://www.tandfonline.com/doi/abs/10.1080/15548627.2021.1933742

DHODH and cancer: promising prospects to be explored – Yue Zhou, Lei Tao, Xia Zhou, Zeping Zuo, Jin Gong, Xiaocong Liu, Yang Zhou, Chunqi Liu, Na Sang, Huan Liu, Jiao Zou, Kun Gou, Xiaowei Yang and Yinglan Zhao. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-021-00250-z

Targeting the Mevalonate Pathway in Cancer – Dennis Juarez and David A. Fruman. https://www.cell.com/trends/cancer/fulltext/S2405-8033(20)30309-5

MicroRNA-mediated regulation of glucose and lipid metabolism – Pamela Agbu and Richard W. Carthew. https://www.nature.com/articles/s41580-021-00354-w

The eIF2α kinase HRI in innate immunity, proteostasis, and mitochondrial stress – Stephen E. Girardin, Camille Cuziol, Dana J. Philpott, Damien Arnoult. https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15553

Pyruvate carboxylase and cancer progression – Violet A. Kiesel, Madeline P. Sheeley, Michael F. Coleman, Eylem Kulkoyluoglu Cotul, Shawn S. Donkin, Stephen D. Hursting, Michael K. Wendt and Dorothy Teegarden. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-021-00256-7

Open questions on the mitochondrial unfolded protein response – Friederike‐Nora Vögtle. https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15569

Metabolic Codependencies in the Tumor Microenvironment – Prasenjit Dey, Alec C. Kimmelman and Ronald A. DePinho. https://cancerdiscovery.aacrjournals.org/content/11/5/1067

Evolving concepts in NAD+ metabolism – Claudia C.S. Chini, Julianna D. Zeidler, Sonu Kashyap, Gina Warner, Eduardo Nunes Chini. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00169-8

Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment? – Megan Jessica McNamee, David Michod and Maria Victoria Niklison-Chirou. https://www.nature.com/articles/s41420-021-00474-4


Comments


Immunotherapy breaches low-sugar dieting of tumor Treg cells – Clarissa Campbell, Alexander Y. Rudensky. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00176-5

More writing: mTORC1 promotes m6A mRNA methylation – Sunil Shetty, Michael N. Hall. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00325-7

When cells are down on their LUC7L2, alternative splicing rewires metabolism for OXPHOS – Aaron A. Hoskins and Timothy W. Rhoads. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00294-X

NRF2 activates macropinocytosis upon autophagy inhibition – Gourish Mondal and Jayanta Debnath. https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00169-0

Autophagy is critical for cysteine metabolism in pancreatic cancer through regulation of SLC7A11 – Subhadip Mukhopadhyay and Alec C. Kimmelman. https://www.tandfonline.com/doi/abs/10.1080/15548627.2021.1922984

A mitochondrial gatekeeper that helps cells escape death by ferroptosis – Javier Garcia-Bermudez and Kıvanç Birsoy. https://www.nature.com/articles/d41586-021-01203-8

Asparagine, a Key Metabolite in Cellular Response to Mitochondrial Dysfunction – Yuyang Liu and Kıvanç Birsoy. https://www.cell.com/trends/cancer/fulltext/S2405-8033(21)00081-9

Breast cancer has a new metabolic Achilles’ heel – Tatiana Alfonso-Pérez, Gabriel Baonza and Fernando Martin-Belmonte. https://www.nature.com/articles/s42255-021-00394-8

Distinct nutrient use in tumors – John F. Foley. https://stke.sciencemag.org/content/14/683/eabj4738

Anti-CTLA4 Perturbs Treg-Based Immunosuppression in Glycolysis-Low Tumorshttps://cancerdiscovery.aacrjournals.org/content/11/5/1003.2

Autophagy-Deficient Pancreatic Cancer Cells Depend on Macropinocytosishttps://cancerdiscovery.aacrjournals.org/content/11/5/OF28

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