MetaboList – March 2021


Nucleotides


5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING – Jingru Tian, Dingyao Zhang, Vadim Kurbatov, Qinrong Wang, Yadong Wang, Dorthy Fang, Lizhen Wu, Marcus Bosenberg, Mandar D Muzumdar, Sajid Khan, Qianjin Lu, Qin Yan, Jun Lu. https://www.embopress.org/doi/abs/10.15252/embj.2020106065

Inhibition of guanosine monophosphate synthetase (GMPS) blocks glutamine metabolism and prostate cancer growth – Qian Wang, Yi F. Guan, Sarah E. Hancock, Kanu Wahi, Michelle van Geldermalsen, Blake K. Zhang, Angel Pang, Rajini Nagarajah, Blossom Mak, Natasha Freidman, Lisa G. Horvath, Nigel Turner, Jeff Holst. https://onlinelibrary.wiley.com/doi/10.1002/path.5665

Rewiring of purine metabolism in response to acidosis stress in glioma stem cells – Xiaoyu Xu, Liping Wang, Qingce Zang, Shanshan Li, Limei Li, Zhixing Wang, Jiuming He, Boqin Qiang, Wei Han, Ruiping Zhang, Xiaozhong Peng and Zeper Abliz. https://www.nature.com/articles/s41419-021-03543-9


Glucose metabolism


The deubiquitinase JOSD2 is a positive regulator of glucose metabolism – Lyudmila Krassikova, Boxi Zhang, Divya Nagarajan, André Lima Queiroz, Merve Kacal, Evangelos Samakidis, Helin Vakifahmetoglu-Norberg and Erik Norberg. https://www.nature.com/articles/s41418-020-00639-1

Citrullination of pyruvate kinase M2 by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation – Sébastien Coassolo, Guillaume Davidson, Luc Negroni, Giovanni Gambi, Sylvain Daujat, Christophe Romier and Irwin Davidson. https://www.nature.com/articles/s41467-021-21960-4

Gluconeogenic enzyme PCK1 deficiency promotes CHK2 O-GlcNAcylation and hepatocellular carcinoma growth upon glucose deprivation – Jin Xiang, Chang Chen, Rui Liu, Dongmei Gou, Lei Chang, Haijun Deng, Qingzhu Gao, Wanjun Zhang, Lin Tuo, Xuanming Pan, Li Liang, Jie Xia, Luyi Huang, Ke Yao, Bohong Wang, Zeping Hu, Ailong Huang, Kai Wang, Ni Tang. https://www.jci.org/articles/view/144703

SGK1 signaling promotes glucose metabolism and survival in extracellular matrix detached cells – Joshua A. Mason, Jordan A. Cockfield, Daniel J. Pape, Hannah Meissner, Michael T. Sokolowski, Taylor C. White, José C. Valentín López, Juan Liu, Xiaojing Liu, Inmaculada Martínez-Reyes, Navdeep S. Chandel, Jason W. Locasale, Zachary T. Schafer. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00135-2

Hexokinase 2 discerns a novel circulating tumor cell population associated with poor prognosis in lung cancer patients – Liu Yang, Xiaowei Yan, Jie Chen, Qiong Zhan, Yingqi Hua, Shili Xu, Ziming Li, Zhuo Wang, Yu Dong, Dongqing Zuo, Min Xue, Yin Tang, Harvey R. Herschman, Shun Lu, Qihui Shi, and Wei Wei. https://www.pnas.org/content/118/11/e2012228118.abstract?etoc

SUMOylation controls the binding of hexokinase 2 to mitochondria and protects against prostate cancer tumorigenesis – Xun Shangguan, Jianli He, Zehua Ma, Weiwei zhang, Yiyi Ji, Kai Shen, Zhiying Yue, Wenyu Li, Zhixiang Xin, Quan Zheng, Ying Cao, Jiahua Pan, Baijun Dong, Jinke Cheng, Qi Wang and Wei Xue. https://www.nature.com/articles/s41467-021-22163-7

A small-molecule pan-class I glucose transporter inhibitor reduces cancer cell proliferation in vitro and tumor growth in vivo by targeting glucose-based metabolism – Pratik Shriwas, Dennis Roberts, Yunsheng Li, Liyi Wang, Yanrong Qian, Stephen Bergmeier, Jennifer Hines, Subhodip Adhicary, Corinne Nielsen and Xiaozhuo Chen. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-021-00248-7

The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis – Xiaoqing Luo, Enze Zheng, Li Wei, Han Zeng, Hong Qin, Xiaoyu Zhang, Meng Liao, Lin Chen, Lei Zhao, Xiong Z. Ruan, Ping Yang and Yaxi Chen. https://www.nature.com/articles/s41419-021-03596-w

Glycogen metabolism is dispensable for tumour progression in clear cell renal cell carcinoma – Hong Xie, Jun Song, Jason Godfrey, Romain Riscal, Nicolas Skuli, Itzhak Nissim and M. Celeste Simon. https://www.nature.com/articles/s42255-021-00367-x

R-2-hydroxyglutarate attenuates aerobic glycolysis in leukemia by targeting the FTO/m6A/PFKP/LDHB axis – Ying Qing, Lei Dong, Lei Gao, Chenying Li, Yangchan Li, Li   Han, Emily Prince, Brandon Tan, Xiaolan Deng, Collin Wetzel, Chao Shen, Min   Gao, Zhenhua Chen, Wei Li, Bin Zhang, Daniel Braas, Johanna ten Hoeve,   Gerardo Javier Sanchez, Huiying Chen, Lai N. Chan, Chun-Wei Chen, David Ann,   Lei Jiang, Markus Müschen, Guido Marcucci, David R. Plas, Zejuan Li, Rui Su, Jianjun Chen. https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30947-3

Basigin drives intracellular accumulation of l-lactate by  harvesting protons and substrate anions – Anna-Lena Köpnick, Annika Jansen, Katharina Geistlinger, Nathan Hugo Epalle, Eric Beitz. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249110


Amino acid metabolism


mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation – Yilei Zhang, Robert V. Swanda, Litong Nie, Xiaoguang Liu, Chao Wang, Hyemin Lee, Guang Lei, Chao Mao, Pranavi Koppula, Weijie Cheng, Jie Zhang, Zhenna Xiao, Li Zhuang, Bingliang Fang, Junjie Chen, Shu-Bing Qian and Boyi Gan. https://www.nature.com/articles/s41467-021-21841-w

Serine Biosynthesis Is a Metabolic Vulnerability in IDH2-Driven Breast Cancer Progression – Georgina D. Barnabas, Joo Sang Lee, Tamar Shami, Michal Harel, Lir Beck, Michael Selitrennik, Livnat Jerby-Arnon, Neta Erez, Eytan Ruppin and Tamar Geiger. https://cancerres.aacrjournals.org/content/81/6/1443

A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer – Lingfan Xu, Yu Yin, Yanjing Li, Xufeng Chen, Yan Chang, Hong Zhang, Juan Liu, James Beasley, Patricia McCaw, Haoyue Zhang, Sarah Young, Jeff Groth, Qianben Wang, Jason W. Locasale, Xia Gao, Dean G. Tang, Xuesen Dong, Yiping He, Daniel George, Hailiang Hu, and Jiaoti Huang. https://www.pnas.org/content/118/13/e2012748118.abstract?etoc

The glutamine antagonist prodrug JHU-083 slows malignant glioma growth and disrupts mTOR signaling – Yamashita AS, da Costa Rosa M, Stumpo V, Rais R, Slusher BS, Riggins GJ.. https://academic.oup.com/noa/article/3/1/vdaa149/5943017

STK11/LKB1 Mutations in NSCLC Are Associated with KEAP1/NRF2-Dependent Radiotherapy Resistance Targetable by Glutaminase Inhibition – Piyada Sitthideatphaiboon, Ana Galan-Cobo, Marcelo V. Negrao, Xiao Qu, Alissa Poteete, Fahao Zhang, Diane D. Liu, Whitney E. Lewis, Haley N. Kemp, Jeff Lewis, Waree Rinsurongkawong, Uma Giri, J. Jack Lee, Jianjun Zhang, Jack A. Roth, Stephen Swisher and John V. Heymach. https://clincancerres.aacrjournals.org/content/27/6/1720


Lipid metabolism


Structure and inhibition mechanism of the human citrate transporter NaCT – David B. Sauer, Jinmei Song, Bing Wang, Jacob K. Hilton, Nathan K. Karpowich, Joseph A. Mindell, William J. Rice and Da-Neng Wang. https://www.nature.com/articles/s41586-021-03230-x

Statins repress hedgehog signaling in medulloblastoma with no bone toxicities – Qianhai Fan, Tingting Gong, Chaonan Zheng, Jessica M. Y. Ng, Jianquan Chen, Cynthia Myers, Harvey Hensley, Tom Curran and Zeng-jie Yang. https://www.nature.com/articles/s41388-021-01701-z

ELOVL5 Is a Critical and Targetable Fatty Acid Elongase in Prostate Cancer – Margaret M. Centenera, Julia S. Scott, Jelle Machiels, Zeyad D. Nassar, Deanna C. Miller, Irene Zinonos, Jonas Dehairs, Ingrid J.G. Burvenich, Giorgia Zadra, Paolo M. Chetta, Clyde Bango, Emma Evergren, Natalie K. Ryan, Joanna L. Gillis, Chui Yan Mah, Terence Tieu, Adrienne R. Hanson, Ryan Carelli, Katarzyna Bloch, Vasilios Panagopoulos, Etienne Waelkens, Rita Derua, Elizabeth D. Williams, Andreas Evdokiou, Anna Cifuentes-Rius, Nicolas H. Voelcker, Ian G. Mills, Wayne D. Tilley, Andrew M. Scott, Massimo Loda, Luke A. Selth, Johannes V. Swinnen and Lisa M. Butler. https://cancerres.aacrjournals.org/content/81/7/1704


Mitochondria


Oxidative phosphorylation enhances the leukemogenic capacity and resistance to chemotherapy of B cell acute lymphoblastic leukemia – Chiqi Chen , Xiaoxin Hao, Xiaoyun Lai, Ligen Liu, Jun Zhu, Hongfang Shao, Dan Huang, Hao Gu, Tinghua Zhang, Zhuo Yu, Li Xie, Xiaocui Zhang, Yi Yang, Jun Xu, Yuzheng Zhao, Zhigang Lu, Junke Zheng. https://advances.sciencemag.org/content/7/11/eabd6280

Integrated Molecular Characterization of Fumarate Hydratase–deficient Renal Cell Carcinoma – Guangxi Sun, Xingming Zhang, Jiayu Liang, Xiuyi Pan, Sha Zhu, Zhenhua Liu, Cameron M. Armstrong, Jianhui Chen, Wei Lin, Banghua Liao, Tianhai Lin, Rui Huang, Mengni Zhang, Linmao Zheng, Xiaoxue Yin, Ling Nie, Pengfei Shen, Jinge Zhao, Haoran Zhang, Jindong Dai, Yali Shen, Zhiping Li, Jiyan Liu, Junru Chen, Jiandong Liu, Zhipeng Wang, Xudong Zhu, Yuchao Ni, Dan Qin, Ling Yang, Yuntian Chen, Qiang Wei, Xiang Li, Qiao Zhou, Haojie Huang, Jin Yao, Ni Chen and Hao Zeng. https://clincancerres.aacrjournals.org/content/27/6/1734

The mitochondrial carrier SFXN1 is critical for complex III integrity and cellular metabolism – Michelle Grace Acoba, Ebru S. Selen Alpergin, Santosh Renuse, Lucía Fernández-del-Río, Ya-Wen Lu, Oleh Khalimonchuk, Catherine F. Clarke, Akhilesh Pandey, Michael J. Wolfgang, Steven M. Claypool. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00183-2

Mitochondrial uncoupler MB1-47 is efficacious in treating hepatic metastasis of pancreatic cancer in murine tumor transplantation models – Amer Alasadi, Bin Cao, Jingjing Guo, Hanlin Tao, Juan Collantes, Victor Tan, Xiaoyang Su, David Augeri and Shengkan Jin. https://www.nature.com/articles/s41388-021-01688-7


Starvation / metabolic stress


Adaptation of pancreatic cancer cells to nutrient deprivation is reversible and requires glutamine synthetase stabilization by mTORC1 – Pei-Yun Tsai, Min-Sik Lee, Unmesh Jadhav, Insia Naqvi, Shariq Madha, Ashley Adler, Meeta Mistry, Sergey Naumenko, Caroline A. Lewis, Daniel S. Hitchcock, Frederick R. Roberts, Peter DelNero, Thomas Hank, Kim C. Honselmann, Vicente Morales Oyarvide, Mari Mino-Kenudson, Clary B. Clish, Ramesh A. Shivdasani, and Nada Y. Kalaany. https://www.pnas.org/content/118/10/e2003014118.abstract?etoc

MAPK signaling regulates c‐MYC for melanoma cell adaptation to asparagine restriction – Gaurav Pathria,  Sachin Verma,  Jun Yin, David A Scott, Ze’ev A Ronai. https://www.embopress.org/doi/abs/10.15252/embr.202051436?campaign=woletoc

Lipid remodeling in response to methionine stress in MDA-MBA-468 triple-negative breast cancer cells – Stacey L Borrego, Johannes Fahrmann, Jue Hou, Da-Wei Lin, Bruce J Tromberg, Oliver Fiehn, Peter Kaiser. https://pubmed.ncbi.nlm.nih.gov/33647277/

LncRNA GIRGL drives CAPRIN1-mediated phase separation to suppress glutaminase-1 translation under glutamine deprivation – Ruijie Wang, Leixi Cao, Rick Francis Thorne, Xu Dong Zhang, Jinming Li, Fengmin Shao, Lirong Zhang, Mian Wu. https://advances.sciencemag.org/content/7/13/eabe5708

Catastrophic ATP loss underlies a metabolic combination therapy tailored for MYCN-amplified neuroblastoma – Krista M. Dalton, Timothy L. Lochmann, Konstantinos V. Floros, Marissa L. Calbert, Richard Kurupi, Giovanna T. Stein, Joseph McClanaghan, Ellen Murchie, Regina K. Egan, Patricia Greninger, Mikhail Dozmorov, Sivapriya Ramamoorthy, Madhavi Puchalapalli, Bin Hu, Lisa Shock, Jennifer Koblinski, John Glod, Sosipatros A. Boikos, Cyril H. Benes, and Anthony C. Faber. https://www.pnas.org/content/118/13/e2009620118.abstract?etoc

NIK promotes metabolic adaptation of glioblastoma cells to bioenergetic stress – Michael L. Kamradt, Ji-Ung Jung, Kathryn M. Pflug, Dong W. Lee, Victor Fanniel and Raquel Sitcheran. https://www.nature.com/articles/s41419-020-03383-z

Structural and functional remodeling of mitochondria as an adaptive response to energy deprivation – Andrey V. Kuznetsov, Sabzali Javadov, Raimund Margreiter, Michael Grimm, Judith Hagenbuchner, Michael J. Ausserlechner. https://www.sciencedirect.com/science/article/abs/pii/S0005272821000268


mTOR / AMPK


Amino acids-Rab1A-mTORC1 signaling controls whole-body glucose homeostasis – Xin Zhang, Xiaowen Wang, Ziqiang Yuan, Sarah J. Radford, Chen Liu, Steven K. Libutti, X.F. Steven Zheng. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00144-3

Rheb mediates neuronal-activity-induced mitochondrial energetics through mTORC1-independent PDH activation – Wanchun Yang, Dejiang Pang, Mina Chen, Chongyangzi Du, Lanlan Jia, Luoling Wang, Yunling He, Wanxiang Jiang, Liping Luo, Zongyan Yu, Mengqian Mao, Qiuyun Yuan, Ping Tang, Xiaoqiang Xia, Yiyuan Cui, Bo Jing, Alexander Platero, Yanhui Liu, Yuquan Wei, Paul F. Worley, Bo Xiao. https://www.cell.com/developmental-cell/fulltext/S1534-5807(21)00162-3

AMPK-dependent phosphorylation is required for transcriptional activation of TFEB and TFE3 – Mathieu Paquette, Leeanna El-Houjeiri, Linda C. Zirden, Pietri Puustinen, Paola Blanchette, Hyeonju Jeong, Kurt Dejgaard, Peter M. Siegel and Arnim Pause. https://www.tandfonline.com/doi/abs/10.1080/15548627.2021.1898748


Hypoxia


Coenzyme Q biosynthesis inhibition induces HIF‐1α stabilization and metabolic switch toward glycolysis – Irene Liparulo, Christian Bergamini, Marco Bortolus, Natalia Calonghi, Giuseppe Gasparre, Ivana Kurelac, Luca Masin, Nicola Rizzardi, Michela Rugolo, Wenping Wang, Serena J. Aleo, Alisar Kiwan, Cristian Torri, Claudia Zanna, Romana Fato. https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.15561

The ER stress response mediator ERO1 triggers cancer metastasis by favoring the angiogenic switch in hypoxic conditions – Ersilia Varone, Alessandra Decio, Alexander Chernorudskiy, Lucia Minoli, Laura Brunelli, Federica Ioli, Arianna Piotti, Roberta Pastorelli, Maddalena Fratelli, Marco Gobbi, Raffaella Giavazzi and Ester Zito. https://www.nature.com/articles/s41388-021-01659-y


Cancer Immunometabolism


Polyamines drive myeloid cell survival by buffering intracellular pH to promote immunosuppression in glioblastoma – Jason Miska, Aida Rashidi, Catalina Lee-Chang, Peng Gao, Aurora Lopez-Rosas, Peng Zhang, Rachel Burga, Brandyn Castro, Ting Xiao, Yu Han, David Hou, Samay Sampat, Alex Cordero, Joshua S. Stoolman, Craig M. Horbinski, Mark Burns, Yana K. Reshetnyak, Navdeep S. Chandel, and Maciej S. Lesniak.  https://advances.sciencemag.org/content/7/8/eabc8929

Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma – Man Hsin Hung, Joo Sang Lee, Chi Ma, Laurence P. Diggs, Sophia Heinrich, Ching Wen Chang, Lichun Ma, Marshonna Forgues, Anuradha Budhu, Jittiporn Chaisaingmongkol, Mathuros Ruchirawat, Eytan Ruppin, Tim F. Greten and Xin Wei Wang. https://www.nature.com/articles/s41467-021-21804-1

Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy – Xia Liu, Celine L. Hartman, Lingyun Li, Carolyn J. Albert, Fusheng Si, Aiqin Gao, Lan Huang, Yangjing Zhao, Wenli Lin, Eddy C. Hsueh, Lizong Shen, Qixiang Shao, Daniel F. Hoft, David A. Ford, Guangyong Peng. https://stm.sciencemag.org/content/13/587/eaaz6314

Hypoxia-inducible factor activity promotes antitumor effector function and tissue residency by CD8+ T cells – Ilkka Liikanen, Colette Lauhan, Sara Quon, Kyla Omilusik, Anthony T. Phan, Laura Barceló Bartrolí, Amir Ferry, John Goulding, Joyce Chen, James P. Scott-Browne, Jason T. Yustein, Nicole E. Scharping, Deborah A. Witherden, and Ananda W. Goldrath. https://www.jci.org/articles/view/143729


Miscellaneous


MYCN-Amplified Neuroblastoma Is Addicted to Iron and Vulnerable to Inhibition of the System Xc-/Glutathione Axis – Konstantinos V. Floros, JinYang Cai, Sheeba Jacob, Richard Kurupi, Carter K. Fairchild, Mayuri Shende, Colin M. Coon, Krista M. Powell, Benjamin R. Belvin, Bin Hu, Madhavi Puchalapalli, Sivapriya Ramamoorthy, Kimberly Swift, Janina P. Lewis, Mikhail G. Dozmorov, John Glod, Jennifer E. Koblinski, Sosipatros A. Boikos and Anthony C. Faber. https://cancerres.aacrjournals.org/content/81/7/1896

Plasma metabolites to profile pathways in noncommunicable disease multimorbidity – Maik Pietzner, Isobel D. Stewart, Johannes Raffler, Kay-Tee Khaw, Gregory A. Michelotti, Gabi Kastenmüller, Nicholas J. Wareham and Claudia Langenberg. https://www.nature.com/articles/s41591-021-01266-0


Reviews / comments


Amino Acid Depletion Therapies: Starving Cancer Cells to Death – Miriam Butler, Laurens T. van der Meer, Frank N. van Leeuwen. https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(21)00049-7

The metabolic landscape of RAS-driven cancers from biology to therapy – Suman Mukhopadhyay, Matthew G. Vander Heiden and Frank McCormick. https://www.nature.com/articles/s43018-021-00184-x

Cellular metabolism in the defense against microbes – Lena Pernas. http://jcs.biologists.org/content/134/5/jcs252023?etoc

Mitochondrial quality control: from molecule to organelle – Alba Roca-Portoles and Stephen W. G. Tait. https://link.springer.com/article/10.1007/s00018-021-03775-0

Nicotinamide N-methyltransferase: At the crossroads between cellular metabolism and epigenetic regulation – Annalisa Roberti, Agustín F. Fernández, Mario F. Fraga. https://www.sciencedirect.com/science/article/pii/S2212877821000053

Therapeutic targeting of the mitochondrial one-carbon pathway: perspectives, pitfalls, and potential – Li Na Zhao, Mikael Björklund, Matias J. Caldez, Jie Zheng and Philipp Kaldis. https://www.nature.com/articles/s41388-021-01695-8

A cancerous connection for creatine –  Wei Wong. https://stke.sciencemag.org/content/14/676/eabi7099

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