Article
Oncology
Angela Tramonti, Elisabet Cuyas, Jose Encinar, Matthias Pietzke, Alessio Paone, Sara Verdura, Aina Arbusa, Begona Martin-Castillo, Giorgio Giardina, Jorge Joven, Alexei Vazquez, Roberto Contestabile, Francesca Cutruzzola, Javier Menendez
Summary: Metformin functions as a novel non-catalytic inhibitor of SHMT2 by disrupting the PLP-dependent oligomerization process, which could lead to the development of novel SHMT2 inhibitors.
Review
Biochemistry & Molecular Biology
Li Na Zhao, Mikael Bjorklund, Matias J. Caldez, Jie Zheng, Philipp Kaldis
Summary: Most cancer drugs have significant side effects, so understanding the biology of drug targets is crucial for developing more effective treatments. The folate-mediated one-carbon (1C) metabolism pathway has shown promise in reducing side effects. Research suggests that MTHFD2 is a good drug target in this pathway and highlights the potential of other targets as well.
Editorial Material
Cell Biology
Mickie Bhatia, Amro Elrafie
Summary: In this study, Liu et al. show that Prmt7 can regulate the onset and progression of leukemia by inhibiting the self-renewal capacity of leukemic stem cells (LSCs) in a mouse model of chronic myeloid leukemia (CML).
Review
Endocrinology & Metabolism
Shauni L. Geeraerts, Elien Heylen, Kim De Keersmaecker, Kim R. Kampen
Summary: Cancer cells reprogram their metabolism to hyperactivate serine and glycine synthesis, relying on de novo production and genetic alterations to enhance their survival and proliferation. Serine and glycine synthesis play a crucial role in cancer progression, contributing to macromolecule synthesis, oxidative stress neutralization, and regulation of biological processes like methylation.
Article
Cell Biology
Won Dong Lee, Anna Chiara Pirona, Boris Sarvin, Alon Stern, Keren Nevo-Dinur, Elazar Besser, Nikita Sarvin, Shoval Lagziel, Dzmitry Mukha, Shachar Raz, Elina Aizenshtein, Tomer Shlomi
Summary: The study showed that under physiological folate levels in the cell environment, cytosolic serine-hydroxymethyltransferase (SHMT1) is the main source of 1C units in various cancers, while mitochondrial 1C flux is excessively suppressed. Tumor-specific reliance on cytosolic 1C flux is associated with poor capacity to retain intracellular folates, determined by the expression of SLC19A1.
Article
Chemistry, Organic
Zi-Wang Wei, Haruka Niikura, Menghua Wang, Katherine S. Ryan
Summary: This study reports the biosynthetic gene cluster of Azaserine (1) from Glycomyces harbinensis and provides evidence from isotopic feeding, gene deletion, and biochemical experiments for a pathway involving hydrazinoacetic acid (2) and a peptidyl carrier protein-loaded serine (3) as intermediates to the final natural product 1.
Article
Oncology
Nora Pallmann, Ke Deng, Marte Livgard, Martina Tesikova, Yixin Jin, Nicolai Sebastian Frengen, Nermin Kahraman, Hamada M. Mokhlis, Bulent Ozpolat, Wanja Kildal, Havard Emil Danielsen, Ladan Fazli, Paul S. Rennie, Partha P. Banerjee, Aykut Uren, Yang Jin, Omer F. Kuzu, Fahri Saatcioglu
Summary: In prostate cancer cells, activating transcription factor 4 (ATF4) exclusively activates gene expression involved in the mitochondrial (m1C) one-carbon cycle, not the cytoplasmic (c1C) cycle; knockdown of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) inhibits prostate cancer cell growth significantly. This suggests that the m1C cycle plays a key role in prostate cancer progression and may serve as a potential biomarker and therapeutic target.
Article
Oncology
Adam J. Sugarman, Luong Do Huynh, Aidin Shabro, Antonio Di Cristofano
Summary: Anaplastic thyroid cancer (ATC) is an aggressive and lethal tumor, characterized by loss of differentiation, high proliferation rate, and resistance to therapy. The upregulation of the one-carbon metabolic pathway in ATC cells, which generates nucleotides and glycine, was identified as a vulnerability that can be targeted for therapy. Inhibition of the key enzyme SHMT2 in this pathway led to glycine auxotrophy and significant inhibition of cell proliferation, especially in the presence of physiological levels of folates.
Article
Biochemistry & Molecular Biology
Aida Corrillero Bravo, Maria Nieves Ligero Aguilera, Nahuel R. Marziali, Lennart Moritz, Victoria Wingert, Katharina Klotz, Anke Schumann, Sarah C. Gruenert, Ute Spiekerkoetter, Urs Berger, Ann-Kathrin Lederer, Roman Huber, Luciana Hannibal
Summary: S-adenosylmethionine (SAM) is essential for methyl transfer reactions. SAM is produced de novo via the methionine cycle. The demethylation of SAM produces S-adenosylhomocysteine (SAH), an inhibitor of methyltransferases. Measurement of SAM and SAH in plasma is valuable for diagnosing inborn errors of metabolism and assessing methyl group homeostasis.
Article
Medicine, Research & Experimental
Yajuan Zhang, Hua Yu, Jie Zhang, Hong Gao, Siyao Wang, Shuxian Li, Ping Wei, Ji Liang, Guanzhen Yu, Xiongjun Wang, Xinxiang Li, Dawei Li, Weiwei Yang
Summary: This study revealed a new role of SAM in promoting tumor metastasis through PHGDH activity regulation by monoubiquitination in colorectal cancer cells. The increased levels of SAM led to upregulation of cell adhesion genes, promoting tumor cell migration and CRC metastasis. Interestingly, SAM levels correlated with metastatic recurrence in CRC patients.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Endocrinology & Metabolism
Alanna C. Green, Petra Marttila, Nicole Kiweler, Christina Chalkiadaki, Elisee Wiita, Victoria Cookson, Antoine Lesur, Kim Eiden, Francois Bernardin, Karl S. A. Vallin, Sanjay Borhade, Maeve Long, Elahe Kamali Ghahe, Julio J. Jimenez-Alonso, Ann-Sofie Jemth, Olga Loseva, Oliver Mortusewicz, Marianne Meyers, Elodie Viry, Annika I. Johansson, Ondrej Hodek, Evert Homan, Nadilly Bonagas, Louise Ramos, Lars Sandberg, Morten Frodin, Etienne Moussay, Ana Slipicevic, Elisabeth Letellier, Jerome Paggetti, Claus Storgaard Sorensen, Thomas Helleday, Martin Henriksson, Johannes Meiser
Summary: Cancer cells upregulate 1C metabolism to meet their increased need for nucleotides. TH9619 selectively kills cancer cells by targeting nuclear MTHFD2 but not inhibiting mitochondrial MTHFD2. This leads to the accumulation of 10-formyl-tetrahydrofolate and thymidylate depletion, resulting in the death of MTHFD2-expressing cancer cells. This study uncovers a new folate trapping mechanism and provides insights into targeting cancer through 1C metabolism.
Review
Plant Sciences
Mutsumi Watanabe, Yukako Chiba, Masami Yokota Hirai
Summary: The review discusses the metabolism and regulatory functions of key metabolites in the plant metabolic network related to sulfur-containing amino acids and compares them with microbial and animal metabolism, highlighting specific differences in plant metabolism.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
T. Pongnopparat, G. Tingley, Y. Gao, J. T. Brosnan, M. E. Brosnan, S. L. Christian
Summary: The oncogenic RasV12 significantly increases formate overflow, potentially providing a way for tumor cells to produce one-carbon units required for enhanced proliferation.
Article
Biochemistry & Molecular Biology
Connor Quinn, Mario C. Rico, Carmen Merali, Salim Merali
Summary: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide, with a percentage of patients developing nonalcoholic steatohepatitis (NASH). This study investigates the reduction of GNMT protein levels in the liver of NASH patients and explores its impact on disease progression. The findings suggest that decreased GNMT leads to an increase in AdoMet, which contributes to NASH pathogenesis through altered transmethylation and polyamine synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Sijing Pan, Ming Fan, Zhangnan Liu, Xia Li, Huijuan Wang
Summary: Serine/glycine biosynthesis and one-carbon metabolism play crucial roles in sustaining cancer cell survival and proliferation by providing essential macromolecules and maintaining redox balance in the tumor microenvironment. Understanding the regulatory mechanisms of key enzymes and intermediates in these pathways may lead to new opportunities for cancer drug development, dietary interventions, and biomarker identification.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2021)