MetaboList – February 2022


Reviews


The hallmarks of cancer metabolism: Still emerging – Natalya N. Pavlova, Jiajun Zhu, Craig B. Thompson. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00022-5

Metabolic programs tailor T cell immunity in viral infection, cancer, and aging – Sofie Hedlund Møller, Pei-Chun Hsueh, Yi-Ru Yu, Lianjun Zhang, Ping-Chih Ho. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00047-X

Clinical development of metabolic inhibitors for oncology – Kathryn M Lemberg, Sadakatali S Gori, Takashi Tsukamoto, Rana Rais, Barbara S Slusher. https://www.jci.org/articles/view/148550

Diet, lipids, and antitumor immunity – Hannah Prendeville and Lydia Lynch. https://www.nature.com/articles/s41423-021-00781-x

Systems approaches to understand oxygen sensing: how multi-omics has driven advances in understanding oxygen-based signalling – Michael Batie, Niall S. Kenneth, Sonia Rocha. https://portlandpress.com/biochemj/article/479/3/245/230736

Persister cancer cells: Iron addiction and vulnerability to ferroptosis – Raphaël Rodriguez, Stuart L. Schreiber, Marcus Conrad. https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)01038-8

Interleukin 6 as an energy allocator in muscle tissue – Timothy M. Kistner, Bente K. Pedersen and Daniel E. Lieberman. https://www.nature.com/articles/s42255-022-00538-4


Starvation/metformin


Lysosomal cystine mobilization shapes the response of TORC1 and tissue growth to fasting – Patrick Jouandin, Zvonimir Marelja, Yung-Hsin Shih, Andrey A. Parkhitko, Miriam Dambowsky, John M. Asara, Ivan Nemazanyy, Christian C. Dibble, Matias Simons, Norbert Perrimon. https://www.science.org/doi/abs/10.1126/science.abc4203

Low-dose metformin targets the lysosomal AMPK pathway through PEN2 – Teng Ma, Xiao Tian, Baoding Zhang, Mengqi Li, Yu Wang, Chunyan Yang, Jianfeng Wu, Xiaoyan Wei, Qi Qu, Yaxin Yu, Shating Long, Jin-Wei Feng, Chun Li, Cixiong Zhang, Changchuan Xie, Yaying Wu, Zheni Xu, Junjie Chen, Yong Yu, Xi Huang, Ying He, Luming Yao, Lei Zhang, Mingxia Zhu, Wen Wang, Zhi-Chao Wang, Mingliang Zhang, Yuqian Bao, Weiping Jia, Shu-Yong Lin, Zhiyun Ye, Hai-Long Piao, Xianming Deng, Chen-Song Zhang and Sheng-Cai Lin. https://www.nature.com/articles/s41586-022-04431-8

Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis – Traci E. LaMoia,  Gina M. Butrico,  Hasini A. Kalpage,  Leigh Goedeke,  Brandon T. Hubbard,  Daniel F. Vatner,  Rafael C. Gaspar,  Xian-Man Zhang,  Gary W. Cline, Keita Nakahara, Seungwan Woo,  Atsuhiro Shimada,  Maik Hüttemann and Gerald I. Shulman. https://www.pnas.org/doi/10.1073/pnas.2122287119

An AMPKα2-specific phospho-switch controls lysosomal targeting for activation – Kaitlin R. Morrison, William J. Smiles, Naomi X.Y. Ling, Ashfaqul Hoque, Gabrielle Shea, Kevin R.W. Ngoei, Dingyi Yu, Lisa Murray-Segal, John W. Scott, Sandra Galic, Bruce.E. Kemp, Janni Petersen, Jonathan S. Oakhill. https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00086-9

SWI/SNF senses carbon starvation with a pH-sensitive low complexity sequence – J Ignacio Gutierrez, Gregory P Brittingham, Yonca B Karadeniz, Kathleen D Tran, Arnob Dutta, Alex S Holehouse, Craig L Peterson, Liam J Holt. https://elifesciences.org/articles/70344


Macropinocytosis


GCN2 adapts protein synthesis to scavenging-dependent growth – Michel Nofal, Tim Wang, Lifeng Yang, Connor S.R. Jankowski, Sophia Hsin-Jung Li, Seunghun Han, Lance Parsons, Alexander N. Frese, Zemer Gitai, Tracy G. Anthony, Martin Wühr, David M. Sabatini, Joshua D. Rabinowitz. https://www.cell.com/cell-systems/fulltext/S2405-4712(21)00382-3

A low amino acid environment promotes cell macropinocytosis through the YY1-FGD6 axis in Ras-mutant pancreatic ductal adenocarcinoma – Yi-Fan Zhang, Qing Li, Pei-Qi Huang, Tong Su, Shu-Heng Jiang, Li-Peng Hu, Xue-Li Zhang, Yue Sun, Hong Pan, Xiao-Mei Yang, Jun Li, Yan-Zhi Gai, Lei Zhu, Lin-Li Yao, Dong-Xue Li, Yong-Wei Sun, Zhi-Gang Zhang, De-Jun Liu, Yan-Li Zhang and Hui-Zhen Nie. https://www.cell.com/cell-systems/fulltext/S2405-4712(21)00382-3

Hypoxia-induced macropinocytosis represents a metabolic route for liver cancer – Misty Shuo Zhang, Jane Di Cui, Derek Lee, Vincent Wai-Hin Yuen, David Kung-Chun Chiu, Chi Ching Goh, Jacinth Wing-Sum Cheu, Aki Pui-Wah Tse, Macus Hao-Ran Bao, Bowie Po Yee Wong, Carrie Yiling Chen, Chun-Ming Wong, Irene Oi-Lin Ng and Carmen Chak-Lui Wong. https://www.nature.com/articles/s41467-022-28618-9


Pentose phosphate/glucosamines


Metabolic profiling of prostate cancer in skeletal microenvironments identifies G6PD as a key mediator of growth and survival – Jessica Whitburn, Srinivasa R. Rao, Emma V. Morris, Sho Tabata, Akiyoshi Hirayama, Tomoyoshi Soga, James R. Edwards, Zeynep Kaya, Charlotte Palmer, Freddie C. Hamdy, Claire M. Edwards. https://www.science.org/doi/full/10.1126/sciadv.abf9096

Oxidative pentose phosphate pathway controls vascular mural cell coverage by regulating extracellular matrix composition – Nicola Facchinello, Matteo Astone, Matteo Audano, Roxana E. Oberkersch, Marianna Spizzotin, Enrica Calura, Madalena Marques, Mihaela Crisan, Nico Mitro and Massimo M. Santoro. https://www.nature.com/articles/s42255-021-00514-4

Loss of glucose 6-phosphate dehydrogenase function increases oxidative stress and glutaminolysis in metastasizing melanoma cells – Arin B. Aurora, Vishal Khivansara, Ashley Leach, Jennifer G. Gill, Misty Martin-Sandoval, Chendong Yang, Stacy Y. Kasitinon, Divya Bezwada, Alpaslan Tasdogan, Wen Gu, Thomas P. Mathews, Zhiyu Zhao, Ralph J. DeBerardinis, and Sean J. Morrison. https://www.pnas.org/content/119/6/e2120617119.abstract?etoc

The POU2F1-ALDOA axis promotes the proliferation and chemoresistance of colon cancer cells by enhancing glycolysis and the pentose phosphate pathway activity – Jinguan Lin, Longzheng Xia, Linda Oyang, Jiaxin Liang, Shiming Tan, Nayiyuan Wu, Pin Yi, Qing Pan, Shan Rao, Yaqian Han, Yanyan Tang, Min Su, Xia Luo, Yiqing Yang, Xiaohui Chen, Lixia Yang, Yujuan Zhou and Qianjin Liao. https://www.nature.com/articles/s41388-021-02148-y

GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosamine pathway – Virginia Kroef, Sabine Ruegenberg, Moritz Horn, Kira Allmeroth, Lena Ebert, Seyma Bozkus, Stephan Miethe, Ulrich Elling, Bernhard Schermer, Ulrich Baumann, Martin Sebastian Denzel. https://elifesciences.org/articles/69223


Glucose metabolism


Glucagon signaling via supraphysiologic GCGR can reduce cell viability without stimulating gluconeogenic gene expression in liver cancer cells – Jason Godfrey, Romain Riscal, Nicolas Skuli and M. Celeste Simon. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-022-00280-1

PGK1 contributes to tumorigenesis and sorafenib resistance of renal clear cell carcinoma via activating CXCR4/ERK signaling pathway and accelerating glycolysis – Yu He, Xixi Wang, Weiliang Lu, Dan Zhang, Lan Huang, Yang Luo, Li Xiong, Haocheng Li, Peng Zhang, Qiu Li and Shufang Liang. https://www.nature.com/articles/s41419-022-04576-4

D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1 – Ruonan Zhang, Yajing Yang, Wenjing Dong, Mingen Lin, Jing He, Xinchao Zhang, Tongguan Tian, Yunlong Yang, Kun Chen, Qun-Ying Lei, Song Zhang, Yanping Xu, and Lei Lv. https://www.pnas.org/doi/10.1073/pnas.2114851119

PKM2 Is Essential for Bladder Cancer Growth and Maintenance – Yong Xia, Xing Wang, Yan Liu, Ellen Shapiro, Herbert Lepor, Moon-Shong Tang, Tung-Tien Sun, Xue-Ru Wu. https://aacrjournals.org/cancerres/article/82/4/571/678084

Targeting of lactate dehydrogenase C dysregulates the cell cycle and sensitizes breast cancer cells to DNA damage response targeted therapy – Adviti Naik, Julie Decock. https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.13024

Pyruvate dehydrogenase inactivation causes glycolytic phenotype in BAP1 mutant uveal melanoma – Anna Han, Vivian Chua, Usman Baqai, Timothy J. Purwin, Nelisa Bechtel, Emily Hunter, Manoela Tiago, Erin Seifert, David W. Speicher, Zachary T. Schug, J. William Harbour and Andrew E. Aplin. https://www.nature.com/articles/s41388-021-02154-0

A non-catalytic scaffolding activity of hexokinase 2 contributes to EMT and metastasis – Catherine S. Blaha, Gopalakrishnan Ramakrishnan, Sang-Min Jeon, Veronique Nogueira, Hyunsoo Rho, Soeun Kang, Prashanth Bhaskar, Alexander R. Terry, Alexandre F. Aissa, Maxim V. Frolov, Krushna C. Patra, R. Brooks Robey and Nissim Hay. https://www.nature.com/articles/s41467-022-28440-3


Amino acids


Increased mitochondrial proline metabolism sustains proliferation and survival of colorectal cancer cells – Saif Sattar Alaqbi, Lynsey Burke, Inna Guterman, Caleb Green, Kevin West, Raquel Palacios-Gallego, Hong Cai, Constantinos Alexandrou, Ni Ni Moe Myint,E mma Parrott,Lynne M. Howells, Jennifer A. Higgins, Donald J. L. Jones, Rajinder Singh, Robert G. Britton, Cristina Tufarelli, Anne Thomas, Alessandro Rufini. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262364

Targeting glutamine metabolism network for the treatment of therapy-resistant prostate cancer – Lingfan Xu, Bing Zhao, William Butler, Huan Xu, Nan Song, Xufeng Chen, J. Spencer Hauck, Xia Gao, Hong Zhang, Jeff Groth, Qing Yang, Yue Zhao, David Moon, Daniel George, Yinglu Zhou, Yiping He and Jiaoti Huang. https://www.nature.com/articles/s41388-021-02155-z

PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer – Amaia Zabala-Letona, Amaia Arruabarrena-Aristorena, Sonia Fernandez-Ruiz, Cristina Viera, Onintza Carlevaris, Amaia Ercilla, Isabel Mendizabal, Teresa Martin, Alice Macchia, Laura Camacho, Mikel Pujana-Vaquerizo, Pilar Sanchez-Mosquera, Verónica Torrano, Natalia Martin-Martin, Patricia Zuniga-Garcia, Mireia Castillo-Martin, Aitziber Ugalde-Olano, Ana Loizaga-Iriarte, Miguel Unda, Jose M. Mato, Edurne Berra, Maria L. Martinez-Chantar and Arkaitz Carracedo. https://www.nature.com/articles/s41389-022-00382-x

Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth – Jiang-Sha Zhao, Shuo Shi, Hai-Yan Qu, Zuzana Keckesova, Zi-Jian Cao, Li-Xian Yang, Xiaofu Yu, Limin Feng, Zhong Shi, Joanna Krakowiak, Ruo-Ying Mao, Yi-Tong Shen, Yu-Meng Fan, Tian-Min Fu, Cunqi Ye, Daqian Xu, Xiaofei Gao, Jia You, Wenbo Li, Tingbo Liang, Zhimin Lu and Yu-Xiong Feng. https://www.nature.com/articles/s42255-021-00524-2


Folate/Nucleotides


Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress – Nadilly Bonagas, Nina M. S. Gustafsson, Martin Henriksson, Petra Marttila, Robert Gustafsson et al. and Thomas Helleday. https://www.nature.com/articles/s43018-022-00331-y

Targeting Ribonucleotide Reductase Induces Synthetic Lethality in PP2A-Deficient Uterine Serous Carcinoma – Caitlin M. O’Connor, Sarah E. Taylor, Kathryn M. Miller, Lauren Hurst, Terrance J. Haanen, Tahra K. Suhan, Kaitlin P. Zawacki, Fallon K. Noto, Jonida Trako, Arathi Mohan, Jaya Sangodkar, Dmitriy Zamarin, Analisa DiFeo, Goutham Narla. https://aacrjournals.org/cancerres/article/82/4/721/678077


Mitochondria / lipids


Ghost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability – Jagadish C. Ghosh, Michela Perego, Ekta Agarwal, Irene Bertolini, Yuan Wang, Aaron R. Goldman, Hsin-Yao Tang, Andrew V. Kossenkov, Catherine J. Libby, Lucia R. Languino, Edward F. Plow, Annamaria Morotti, Luisa Ottobrini, Marco Locatelli, David W. Speicher, M. Cecilia Caino, Joel Cassel, Joseph M. Salvino, Marie E. Robert, Valentina Vaira, and Dario C. Altieri. https://www.pnas.org/doi/10.1073/pnas.2115624119

Combined inhibition of HMGCoA reductase and mitochondrial complex I induces tumor regression of BRAF inhibitor-resistant melanomas – Evelyn de Groot, Sruthy Varghese, Lin Tan, Barbara Knighton, Mary Sobieski, Nghi Nguyen, Yong Sung Park, Reid Powell, Philip L. Lorenzi, Bin Zheng, Clifford Stephan and Y. N. Vashisht Gopal. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-022-00281-0

Malic enzyme 2 maintains protein stability of mutant p53 through 2-hydroxyglutarate – Mengjia Zhao, Pengbo Yao, Youxiang Mao, Jinjun Wu , Weihua Wang, Chenhui Geng, Jie Cheng, Wenjing Du and Peng Jiang. https://www.nature.com/articles/s42255-022-00532-w

SERAC1 is a component of the mitochondrial serine transporter complex required for the maintenance of mitochondrial DNA – Hezhi Fang, Anran Xie, Miaomiao Du, Xueyun Li, Kaiqiang Yang, Yinxu Fu, Xiangshu Yuan, Runxiao Fan, Weidong Yu, Zhuohua Zhou, Tiantian Sang, Ke Nie, Jin Li, Qiongya Zhao, Zhehui Chen, Yanling Yang, Chaoyang Hong, Jianxin Lyu. https://www.science.org/doi/abs/10.1126/scitranslmed.abl6992

Necrotic debris and STING exert therapeutically relevant effects on tumor cholesterol homeostasis – Sampath Katakam,  eSantosh Anand, Patricia Martin, Nicolo Riggi, Ivan Stamenkovic. https://www.life-science-alliance.org/content/5/3/e202101256.abstract?etoc


Cancer Immunometabolism


Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments – Shogo Kumagai, Shohei Koyama, Kota Itahashi, Tokiyoshi Tanegashima, Yi-tzu Lin, Yosuke Togashi, Takahiro Kamada, Takuma Irie, Genki Okumura, Hidetoshi Kono, Daisuke Ito, Rika Fujii, Sho Watanabe, Atsuo Sai, Shota Fukuoka, Eri Sugiyama, Go Watanabe, Takuya Owari, Hitomi Nishinakamura, Daisuke Sugiyama, Yuka Maeda, Akihito Kawazoe, Hiroki Yukami, Keigo Chida, Yuuki Ohara, Tatsuya Yoshida, Yuki Shinno, Yuki Takeyasu, Masayuki Shirasawa, Kenta Nakama, Keiju Aokage, Jun Suzuki, Genichiro Ishii, Takeshi Kuwata, Naoya Sakamoto, Masahito Kawazu, Toshihide Ueno, Taisuke Mori, Naoya Yamazaki, Masahiro Tsuboi, Yasushi Yatabe, Takahiro Kinoshita, Toshihiko Doi, Kohei Shitara, Hiroyuki Mano, Hiroyoshi Nishikawa. https://www.sciencedirect.com/science/article/pii/S1535610822000034

Cancer-cell-derived GABA promotes β-catenin-mediated tumour growth and immunosuppression – De Huang, Yan Wang, J. Will Thompson, Tao Yin, Peter B. Alexander, Diyuan Qin, Poorva Mudgal, Haiyang Wu, Yaosi Liang, Lianmei Tan, Christopher Pan, Lifeng Yuan, Ying Wan, Qi-Jing Li and Xiao-Fan Wang. https://www.nature.com/articles/s41556-021-00820-9

Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity – Kebria Hezaveh, Rahul S. Shinde, Andreas Klötgen, Marie Jo Halaby, Sara Lamorte, M. Teresa Ciudad, Rene Quevedo, Luke Neufeld, Zhe Qi Liu, Robbie Jin, Barbara T. Grünwald, Elisabeth G. Foerster, Danica Chaharlangi, Mengdi Guo, Priya Makhijani, Xin Zhang, Trevor J. Pugh, Devanand M. Pinto, Ileana L. Co, Alison P. McGuigan, Gun Ho Jang, Rama Khokha, Pamela S. Ohashi, Grainne M. O’Kane, Steven Gallinger, William W. Navarre, Heather Maughan, Dana J. Philpott, David G. Brooks, Tracy L. McGaha. https://www.cell.com/immunity/fulltext/S1074-7613(22)00035-8


Miscellaneous


Redox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer – Zuen Ren, Huizhi Liang, Phillip M. Galbo Jr, Malindrie Dharmaratne, Ameya S. Kulkarni, Atefeh Taherian Fard, Marie Louise Aoun, Nuria Martinez-Lopez, Kimita Suyama, Outhiriaradjou Benard, Wei Zheng, Yang Liu, Joseph Albanese, Deyou Zheng, Jessica C. Mar, Rajat Singh, Michael B. Prystowsky, Larry Norton, and Rachel B. Hazan. https://www.pnas.org/doi/10.1073/pnas.2107266119

Integrated Metabolic Profiling and Transcriptional Analysis Reveals Therapeutic Modalities for Targeting Rapidly Proliferating Breast Cancers – Chengheng Liao; Cherise Ryan Glodowski; Cheng Fan; Juan Liu; Kevin R. Mott; Akash Kaushik; Hieu Vu; Jason W. Locasale; Samuel K. McBrayer; Ralph J. DeBerardinis; Charles M. Perou; Qing Zhang. https://aacrjournals.org/cancerres/article/82/4/665/678072

SOX2 mediates metabolic reprogramming of prostate cancer cells – Larischa de Wet, Anthony Williams, Marc Gillard, Steven Kregel, Sophia Lamperis, Lisa C. Gutgesell, Jordan E. Vellky, Ryan Brown, Kelly Conger, Gladell P. Paner, Heng Wang, Elizabeth A. Platz, Angelo M. De Marzo, Ping Mu, Jonathan L. Coloff, Russell Z. Szmulewitz and Donald J. Vander Griend. https://www.nature.com/articles/s41388-021-02157-x

Age-associated decline of MondoA drives cellular senescence through impaired autophagy and mitochondrial homeostasis – Hitomi Yamamoto-Imoto, Satoshi Minami, Tatsuya Shioda, Yurina Yamashita, Shinsuke Sakai, Shihomi Maeda, Takeshi Yamamoto, Shinya Oki, Mizuki Takashima, Tadashi Yamamuro, Kyosuke Yanagawa, Ryuya Edahiro, Miki Iwatani, Mizue So, Ayaka Tokumura, Toyofumi Abe, Ryoichi Imamura, Norio Nonomura, Yukinori Okada, Donald E. Ayer, Hidesato Ogawa, Eiji Hara, Yoshitsugu Takabatake, Yoshitaka Isaka, Shuhei Nakamura, Tamotsu Yoshimori. https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00171-1

Label-free sensing of cells with fluorescence lifetime imaging: The quest for metabolic heterogeneity – Evgeny A. Shirshin, Marina V. Shirmanova, Alexey V. Gayer, Maria M. Lukina, Elena E. Nikonova, Boris P. Yakimov, Gleb S. Budylin, Varvara V. Dudenkova, Nadezhda I. Ignatova, Dmitry V. Komarov, Vladislav V. Yakovlev, Wolfgang Becker, Elena V. Zagaynova, Vladislav I. Shcheslavskiy and Marlan O. Scully. https://www.pnas.org/doi/10.1073/pnas.2118241119

Novel humanized monoclonal antibodies for targeting hypoxic human tumors via two distinct extracellular domains of carbonic anhydrase IX – Miriam Zatovicova, Ivana Kajanova, Monika Barathova, Martina Takacova, Martina Labudova, Lucia Csaderova, Lenka Jelenska, Eliska Svastova, Silvia Pastorekova, Adrian L. Harris and Jaromir Pastorek. https://cancerandmetabolism.biomedcentral.com/articles/10.1186/s40170-022-00279-8


Comments


Rag GTPases regulate cellular amino acid homeostasis – Ken Inoki and Kun-Liang Guan. https://www.pnas.org/doi/10.1073/pnas.2200788119

Immune sensing of microbial metabolites: Action at the tumor – Timothy L. Frankel, Marina Pasca di Magliano. https://www.cell.com/immunity/fulltext/S1074-7613(22)00038-3

Beating cancer one carbon at a time – Vasilis S. Dionellis and Thanos D. Halazonetis. https://www.nature.com/articles/s43018-022-00333-w

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