MetaboList – December 2020

Serine metabolism


In Vivo Evidence for Serine Biosynthesis-Defined Sensitivity of Lung Metastasis, but Not of Primary Breast Tumors, to mTORC1 Inhibition – Gianmarco Rinaldi, Erica Pranzini, Joke Van Elsen, Dorien Broekaert, Cornelius M Funk, Mélanie Planque, Ginevra Doglioni, Patricia Altea-Manzano, Matteo Rossi, Vincent Geldhof, Shao Thing Teoh, Christina Ross, Kent W Hunter, Sophia Y Lunt, Thomas G P Grünewald, Sarah-Maria Fendt. https://www.sciencedirect.com/science/article/abs/pii/S1097276520308273
 
High Fructose Drives the Serine Synthesis Pathway in Acute Myeloid Leukemic Cells – Sangmoo Jeong, Angela Maria Savino, Rachel Chirayil, Ersilia Barin, Yuanming Cheng, Sun-Mi Park , Alexandra Schurer, Edouard Mullarky, Lewis C Cantley, Michael G Kharas, Kayvan R Keshari. https://www.sciencedirect.com/science/article/abs/pii/S1550413120306604?via%3Dihub



Cystine / Glutathione


Non-canonical Glutamate-Cysteine Ligase Activity Protects against Ferroptosis – Yun Pyo Kang, Andrea Mockabee-Macias, Chang Jiang, Aimee Falzone, Nicolas Prieto-Farigua, Everett Stone, Isaac S Harris, Gina M DeNicola. https://www.sciencedirect.com/science/article/abs/pii/S1550413120306628
 
KEAP1/NFE2L2 Mutations Predict Lung Cancer Radiation Resistance That Can Be Targeted by Glutaminase Inhibition – Michael S. Binkley, Young-Jun Jeon, Monica Nesselbush, Everett J. Moding, Barzin Y. Nabet, Diego Almanza, Christian Kunder, Henning Stehr, Christopher H. Yoo, Siyeon Rhee, Michael Xiang, Jacob J. Chabon, Emily Hamilton, David M. Kurtz, Linda Gojenola, Susie Grant Owen, Ryan B. Ko, June Ho Shin, Peter G. Maxim, Natalie S. Lui, Leah M. Backhus, Mark F. Berry, Joseph B. Shrager, Kavitha J. Ramchandran, Sukhmani K. Padda, Millie Das, Joel W. Neal, Heather A. Wakelee, Ash A. Alizadeh, Billy W. Loo Jr and Maximilian Diehn. https://cancerdiscovery.aacrjournals.org/content/10/12/1826
 
Glutathione metabolism is essential for self-renewal and chemoresistance of pancreatic cancer stem cells – Petra Jagust, Sonia Alcalá, Bruno Sainz Jr, Christopher Heeschen, Patricia Sancho. https://www.wjgnet.com/1948-0210/abstract/v12/i11/1410.htm


Glutamine and other amino acids


KRAS-regulated glutamine metabolism requires UCP2-mediated aspartate transport to support pancreatic cancer growth – Susanna Raho, Loredana Capobianco, Rocco Malivindi, Angelo Vozza, Carmela Piazzolla, Francesco De Leonardis, Ruggiero Gorgoglione, Pasquale Scarcia, Francesca Pezzuto, Gennaro Agrimi, Simona N. Barile, Isabella Pisano, Stephan J. Reshkin, Maria R. Greco, Rosa A. Cardone, Vittoria Rago, Yuan Li, Carlo M. T. Marobbio, Wolfgang Sommergruber, Christopher L. Riley, Francesco M. Lasorsa, Edward Mills, Maria C. Vegliante, Giuseppe E. De Benedetto, Deborah Fratantonio, Luigi Palmieri, Vincenza Dolce and Giuseppe Fiermonte. https://www.nature.com/articles/s42255-020-00315-1
 
Endocytosis-Mediated Replenishment of Amino Acids Favors Cancer Cell Proliferation and Survival in Chromophobe Renal Cell Carcinoma – Yi Xiao, Anja Rabien, René Buschow, Vyacheslav Amtislavskiy, Jonas Busch, Ergin Kilic, Sonia L. Villegas, Bernd Timmermann, Moritz Schütte, Thorsten Mielke, Marie-Laure Yaspo, Klaus Jung and David Meierhofer. https://cancerres.aacrjournals.org/content/80/24/5491
 
BCAT1 affects mitochondrial metabolism independently of leucine  transamination in activated human macrophages – Jeong-Hun Ko, Antoni Olona, Adonia E. Papathanassiu, Norzawani Buang,  Kwon-Sik Park, Ana S. H. Costa, Claudio Mauro, Christian Frezza and Jacques Behmoaras. http://jcs.biologists.org/content/133/22/jcs247957?etoc
 
In vivo assessment of glutamine anaplerosis into the TCA cycle in human pre-malignant and malignant clonal plasma cells – Wilson I. Gonsalves, Jin Sung Jang, Erik Jessen, Taro Hitosugi, Laura A. Evans, Dragan Jevremovic, Xuan-Mai Pettersson, Alexander Graham Bush, Jaimee Gransee, Emilie I. Anderson, Shaji K. Kumar and K. Sreekumaran Nair. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-020-00235-4
 


Glucose metabolism


Increased demand for NAD+ relative to ATP drives aerobic glycolysis – Alba Luengo, Zhaoqi Li, Dan Y. Gui, Lucas B. Sullivan, Maria Zagorulya, Brian T. Do, Raphael Ferreira, Adi Naamati, Ahmed Ali, Caroline A. Lewis, Craig J. Thomas, Stefani Spranger, Nicholas J. Matheson, Matthew G. Vander Heiden. https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30904-7
 
HDAC8-dependent deacetylation of PKM2 directs nuclear localization and glycolysis to promote proliferation in hepatocellular carcinoma – Ruixue Zhang, Mengqin Shen, Chunhua Wu, Yumei Chen, Jiani Lu, Jiajin Li, Li Zhao, Huannan Meng, Xiang Zhou, Gang Huang, Xiaoping Zhao and Jianjun Liu. https://www.nature.com/articles/s41419-020-03212-3
 


Lipid metabolism


A metastasis map of human cancer cell lines – Xin Jin, Zelalem Demere, Karthik Nair, Ahmed Ali, Gino B. Ferraro, Ted Natoli, Amy Deik, Lia Petronio, Andrew A. Tang, Cong Zhu, Li Wang, Danny Rosenberg, Vamsi Mangena, Jennifer Roth, Kwanghun Chung, Rakesh K. Jain, Clary B. Clish, Matthew G. Vander Heiden and Todd R. Golub. https://www.nature.com/articles/s41586-020-2969-2
 
Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis – Junmei Yi, Jiajun Zhu, Jiao Wu, Craig B. Thompson, and Xuejun Jiang. https://www.pnas.org/content/117/49/31189.abstract?etoc
 
HCAR1/MCT1 Regulates Tumor Ferroptosis through the Lactate-Mediated AMPK-SCD1 Activity and Its Therapeutic Implications – Youbo Zhao, Menghuan Li, Xuemei Yao, Yang Fei, Zhenghong Lin, Zhengguo Li, Kaiyong Cai, Yanli Zhao, Zhong Luo. https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31476-5
 
Long Noncoding RNA TINCR-Mediated Regulation of Acetyl-CoA Metabolism Promotes Nasopharyngeal Carcinoma Progression and Chemoresistance – Zi-Qi Zheng, Zhi-Xuan Li, Jia-Li Guan, Xu Liu, Jun-Yan Li, Yue Chen, Li Lin, Jia Kou, Jia-Wei Lv, Lu-Lu Zhang, Guan-Qun Zhou, Rui-Qi Liu, FoPing Chen, Xiao-Jun He, Ying-Qin Li, Feng Li, Si-Si Xu, Jun Ma, Na Liu and Ying Sun. https://cancerres.aacrjournals.org/content/80/23/5174

Acetylation-mediated remodeling of the nucleolus regulates cellular acetyl-CoA responses – Ryan Houston,Shiori Sekine,Michael J. Calderon,Fayaz Seifuddin,Guanghui Wang,Hiroyuki Kawagishi,Daniela A. Malide,Yuesheng Li,Marjan Gucek,Mehdi Pirooznia,Alissa J. Nelson,Matthew P. Stokes,Jacob Stewart-Ornstein,Steven J. Mullett,Stacy G. Wendell,Simon C. Watkins,Toren Finkel,Yusuke Sekine. https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000981
 
KRAS Controls Pancreatic Cancer Cell Lipid Metabolism and Invasive Potential through the Lipase HSL – Cody N. Rozeveld, Katherine M. Johnson, Lizhi Zhang and Gina L. Razidlo. https://cancerres.aacrjournals.org/content/80/22/4932

 

Nucleotides and folate



The Folate Cycle Enzyme MTHFR Is a Critical Regulator of Cell Response to MYC-Targeting Therapies – Angela Su, Frank Ling, Camille Vaganay, Gaetano Sodaro, Chaïma Benaksas, Reinaldo Dal Bello, Antoine Forget, Bryann Pardieu, Kevin H. Lin, Justine C. Rutter, Christopher F. Bassil, Gael Fortin, Justine Pasanisi, Iléana Antony-Debré, Gabriela Alexe, Jean-François Benoist, Alain Pruvost, Yana Pikman, Jun Qi, Marie-Hélène Schlageter, Jean-Baptiste Micol, Giovanni Roti, Thomas Cluzeau, Hervé Dombret, Claude Preudhomme, Nina Fenouille, Lina Benajiba, Hava M. Golan, Kimberly Stegmaier, Camille Lobry, Kris C. Wood, Raphael Itzykson and Alexandre Puissant. https://cancerdiscovery.aacrjournals.org/content/10/12/1894
 
Non-metabolic role of UCK2 links EGFR-AKT pathway activation to metastasis enhancement in hepatocellular carcinoma – Jie Cai, Xuehua Sun, Han Guo, Xiaoye Qu, Hongting Huang, Chang Yu, Hailong Wu, Yueqiu Gao, Xiaoni Kong and Qiang Xia. https://www.nature.com/articles/s41389-020-00287-7

 

Mitochondria



Altered mitochondria functionality defines a metastatic cell state in lung cancer and creates an exploitable vulnerability – Chen-Hua Chuang, Madeleine Dorsch, Philip Dujardin, Sukrit Silas, Kristina Ueffing, Johanna M Hölken, Dian Yang, Monte M Winslow  Barbara M Grüner. https://cancerres.aacrjournals.org/content/early/2020/11/25/0008-5472.CAN-20-1865
 
Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import – Enrico Girardi, Gennaro Agrimi, Ulrich Goldmann, Giuseppe Fiume, Sabrina Lindinger, Vitaly Sedlyarov, Ismet Srndic, Bettina Gürtl, Benedikt Agerer, Felix Kartnig, Pasquale Scarcia, Maria Antonietta Di Noia, Eva Liñeiro, Manuele Rebsamen, Tabea Wiedmer, Andreas Bergthaler, Luigi Palmieri and Giulio Superti-Furga. https://www.nature.com/articles/s41467-020-19871-x
 
Estrogen-related receptor alpha directly binds to p53 and cooperatively controls colon cancer growth through the regulation of mitochondrial biogenesis and function – Humberto De Vitto, Joohyun Ryu, Ali Calderon-Aparicio, Josh Monts, Raja Dey, Abhijit Chakraborty, Mee-Hyun Lee, Ann M. Bode and Zigang Dong. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-020-00234-5

BCL(X)L and BCL2 increase the metabolic fitness of breast cancer cells: a single-cell imaging study – Lucantoni F, Salvucci M, Düssmann H, Lindner AU, Lambrechts D, Prehn JHM. https://www.nature.com/articles/s41418-020-00683-x
 


Starvation / Metabolic stress


Protein synthesis inhibitors stimulate MondoA transcriptional activity by driving an accumulation of glucose 6-phosphate – Blake R. Wilde, Mohan R. Kaadige, Katrin P. Guillen, Andrew Butterfield, Bryan E. Welm and Donald E. Ayer. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-020-00233-6

PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability – Sandra M. Martín-Guerrero; Pedro Casado; Maruan Hijazi; Vinothini Rajeeve; Julio Plaza-Díaz; Francisco Abadía-Molina; Julio Navascués; Miguel A. Cuadros; Pedro R. Cutillas; David Martín-Oliva. https://portlandpress.com/biochemj/article-abstract/477/23/4491/226892

 

Hypoxia


Hypoxia Induces Transcriptional and Translational Downregulation of the Type I IFN Pathway in Multiple Cancer Cell Types – Ana Miar, Esther Arnaiz, Esther Bridges, Shaunna Beedie, Adam P. Cribbs, Damien J. Downes, Robert A. Beagrie, Jan Rehwinkel and Adrian L. Harris. https://cancerres.aacrjournals.org/content/80/23/5245
 
 

IDH


Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment – Elavarasan Subramani, Marina Radoul, Chloe Najac, Georgios Batsios, Abigail R. Molloy, Donghyun Hong, Anne Marie Gillespie, Romelyn Delos Santos, Pavithra Viswanath, Joseph F. Costello, Russell O. Pieper and Sabrina M. Ronen. https://cancerres.aacrjournals.org/content/80/22
 
Inhibition of 2-Hydroxyglutarate Elicits Metabolic-reprograming and Mutant IDH1 Glioma Immunity in Mice – Padma Kadiyala, Stephen V. Carney, Jessica C. Gauss, Maria B. Garcia-Fabiani, Santiago Haase, Mahmoud S. Alghamri, Felipe J. Núñez, Yayuan Liu, Minzhi Yu, Ayman W. Taher, Fernando M. Nunez, Dan Li, Marta B. Edwards, Celina G. Kleer, Henry Appelman, Yilun Sun, Lili Zhao, James J. Moon, Anna Schwendeman, Pedro R. Lowenstein, Maria G. Castro. https://www.jci.org/articles/view/139542
 


Cancer Immunometabolism


Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity – Alison E. Ringel, Jefte M. Drijvers, Gregory J. Baker, Alessia  Catozzi, Juan C. García-Cañaveras, Brandon M. Gassaway, Brian C. Miller,  Vikram R. Juneja, Thao H. Nguyen, Shakchhi Joshi, Cong-Hui Yao, Haejin Yoon,  Peter T. Sage, Martin W. LaFleur, Justin D. Trombley, Connor A. Jacobson,  Zoltan Maliga, Steven P. Gygi, Peter K. Sorger, Joshua D. Rabinowitz, Arlene  H. Sharpe, Marcia C. Haigis. https://www.cell.com/cell/fulltext/S0092-8674(20)31526-9
 
De novo synthesis and salvage pathway coordinately regulate polyamine homeostasis and determine T cell proliferation and function – Ruohan Wu , Xuyong Chen, Siwen Kang, Tingting Wang, JN Rashida Gnanaprakasam, Yufeng Yao, Lingling Liu, Gaofeng Fan, Mark R. Burns, Ruoning Wang. https://advances.sciencemag.org/content/6/51/eabc4275/tab-article-info
 
Lactate Limits T Cell Proliferation via the NAD(H) Redox State – William J. Quinn III, Jing Jiao, Tara TeSlaa, Jason Stadanlick, Zhonglin Wang, Liqing Wang, Tatiana Akimova, Alessia Angelin, Patrick M. Schäfer, Michelle D. Cully, Caroline Perry, Piotr K. Kopinski, Lili Guo, Ian A. Blair, Louis R. Ghanem, Michael S. Leibowitz, Wayne W. Hancock, Edmund K. Moon, Matthew H. Levine, Evgeniy B. Eruslanov, Douglas C. Wallace, Joseph A. Baur, Ulf H. Beier. https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31489-3
 
The glutaminase inhibitor CB-839 (Telaglenastat) enhances the anti-melanoma activity of T cell mediated immunotherapies – Sruthy Varghese, Snigdha Pramanik, Leila J. Williams, Hannah R Hodges, Courtney W Hudgens, Grant M. Fischer, Catherine K Luo, Barbara Knighton, Lin Tan, Philip L. Lorenzi, Andrew L. MacKinnon, Jennifer L. McQuade, Yared Hailemichael, Jason Roszik, Weiyi Peng and Y.N. Vashisht Gopal. https://mct.aacrjournals.org/content/early/2020/12/23/1535-7163.MCT-20-0430.long
 


Miscellaneous


3D Culture Models with CRISPR Screens Reveal Hyperactive NRF2 as a Prerequisite for Spheroid Formation via Regulation of Proliferation and Ferroptosis – Nobuaki Takahashi, Patricia Cho, Laura M. Selfors, Hendrik J. Kuiken, Roma Kaul, Takuro Fujiwara, Isaac S. Harris, Tian Zhang, Steven P. Gygi, Joan S. Brugge. https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30693-6

The Associations of Aspirin, Statins, and Metformin With Lung Cancer Risk and Related Mortality: A Time-Dependent Analysis of Population-Based Nationally Representative Data – Jihun Kang, Su-Min Jeong, Dong Wook Shin, Mihee Cho, Jong Ho Cho, Jehun Kim. https://www.jto.org/article/S1556-0864(20)30712-7/fulltext
 


Reviews


Targeting Metabolic Plasticity and Flexibility Dynamics for Cancer Therapy – Sarah-Maria Fendt, Christian Frezza and Ayelet Erez. https://cancerdiscovery.aacrjournals.org/content/10/12/1797

The Bidirectional Relationship Between Cancer Epigenetics and Metabolism – Luke T. Izzo, Hayley C. Affronti, and Kathryn E. Wellen. Annual Review of Cancer Biology. https://www.annualreviews.org/doi/abs/10.1146/annurev-cancerbio-070820-035832

Crosstalk between mechanotransduction and metabolism – Patrizia Romani, Lorea Valcarcel-Jimenez, Christian Frezza and Sirio Dupont. https://www.nature.com/articles/s41580-020-00306-w

Metabolic Coordination of Cell Fate by α-Ketoglutarate-Dependent Dioxygenases – Sanjeethan C. Baksh, Lydia W.S. Finley. https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(20)30190-2

Hypoxia Dictates Metabolic Rewiring of Tumors: Implications for Chemoresistance – Belisario, D.C.; Kopecka, J.; Pasino, M.; Akman, M.; De Smaele, E.; Donadelli, M.; Riganti, C. https://www.mdpi.com/2073-4409/9/12/2598

The Metabolic Underpinnings of Ferroptosis – Jiashuo Zheng, Marcus Conrad. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30544-1

Iron: An Essential Element of Cancer Metabolism – Myriam Y. Hsu, Erica Mina, Antonella Roetto and Paolo E. Porporato. https://www.mdpi.com/2073-4409/9/12/2591

Fructose Metabolism in Cancer – Nils Krause and Andre Wegner. https://www.mdpi.com/2073-4409/9/12/2635

The p53 Pathway and Metabolism: The Tree That Hides the Forest – Airelle Lahalle, Matthieu Lacroix, Carlo De Blasio, Madi Y. Cissé, Laetitia K. Linaresand Laurent Le Cam. https://www.mdpi.com/2072-6694/13/1/133#abstract
 


Comments


Fighting for Fat: Gluttonous Tumors and Starved T Cells – Joshua H. Goodman, Anthony W. Ferrante Jr. https://www.cell.com/cell/fulltext/S0092-8674(20)31611-1

Mind your media – Shoval Lagziel, Eyal Gottlieb and Tomer Shlomi. https://www.nature.com/articles/s42255-020-00299-y

Tumor start‐up: mitochondrial fusion makes it happen – Ana R Rebelo, Marcia Garcez, Catarina CF Homem. https://www.embopress.org/doi/abs/10.15252/embj.2020106927

O-Mg! Lactate Drives Mg2+ Mobilization – Blake R. Wilde, Heather R. Christofk. https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30801-7

The Center Cannot Hold: NRF2 Battles Ferroptosis in the 3rd Dimension – Warren L. Wu, Thales Papagiannakopoulos. https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30800-5

One Metformin a Day, Keeps Lung Cancer Away! Or Does It? – Samira Shojaee, Patrick Nana-Sinkam. https://www.jto.org/article/S1556-0864(20)30811-X/fulltext

Neutrophils Provide Lipids to Metastatic Tumor Cells, Fueling Growthhttps://cancerdiscovery.aacrjournals.org/content/10/12/OF9

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