Oncogenic Integration of Nucleotide Metabolism via Fatty Acid Synthase in Non-Hodgkin Lymphoma

Metabolic dysfunctions enabling increased nucleotide biosynthesis are necessary for supporting malignant proliferation. Our investigations indicate that upregulation of fatty acid synthase (FASN) and de novo lipogenesis, commonly observed in many cancers, are associated with nucleotide metabolic dys...

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Published in:	Frontiers in oncology Vol. 11; p. 725137
Main Authors:	Ravi, Dashnamoorthy, Beheshti, Afshin, Abermil, Nasséra, Lansigan, Frederick, Kinlaw, William, Matthan, Nirupa R., Mokhtar, Maisarah, Passero, Frank C., Puliti, Patrick, David, Kevin A., Dolnikowski, Gregory G., Su, Xiaoyang, Chen, Ying, Bijan, Mahboubi, Varshney, Rohan R., Kim, Baek, Dave, Sandeep S., Rudolph, Michael C., Evens, Andrew M.
Format:	Journal Article
Language:	English
Published:	Ames Research Center Frontiers Media 26.10.2021 Frontiers Media S.A
Subjects:	Aerospace Medicine FASN Human health and pathology Life Sciences lipid metabolism metabolomics non-Hodgkin lymphoma nucleotides Oncology pentose phosphate pathway Lipid Metabolism Non-Hodgkin Lymphoma Nucleotides Fasn, Metabolomics Pentose Phosphate Pathway non-Hodgkin lymphoma metabolomics nucleotides FASN pentose phosphate pathway lipid metabolism
ISSN:	2234-943X, 2234-943X
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Abstract	Metabolic dysfunctions enabling increased nucleotide biosynthesis are necessary for supporting malignant proliferation. Our investigations indicate that upregulation of fatty acid synthase (FASN) and de novo lipogenesis, commonly observed in many cancers, are associated with nucleotide metabolic dysfunction in lymphoma. The results from our experiments showed that ribonucleotide and deoxyribonucleotide pool depletion, suppression of global RNA/DNA synthesis, and cell cycle inhibition occurred in the presence of FASN inhibition. Subsequently, we observed that FASN inhibition caused metabolic blockade in the rate-limiting step of the oxidative branch of the pentose phosphate pathway (oxPPP) catalyzed by phosphogluconate dehydrogenase (PGDH). Furthermore, we determined that FASN inhibitor treatment resulted in NADPH accumulation and inhibition of PGDH enzyme activity. NADPH is a cofactor utilized by FASN, also a known allosteric inhibitor of PGDH. Through cell-free enzyme assays consisting of FASN and PGDH, we delineated that the PGDH-catalyzed ribulose-5-phosphate synthesis is enhanced in the presence of FASN and is suppressed by increasing concentrations of NADPH. Additionally, we observed that FASN and PGDH were colocalized in the cytosol. The results from these experiments led us to conclude that NADP–NADPH turnover and the reciprocal stimulation of FASN and PGDH catalysis are involved in promoting oxPPP and nucleotide biosynthesis in lymphoma. Finally, a transcriptomic analysis of non-Hodgkin’s lymphoma (n = 624) revealed the increased expression of genes associated with metabolic functions interlinked with oxPPP, while the expression of genes participating in oxPPP remained unaltered. Together we conclude that FASN–PGDH enzymatic interactions are involved in enabling oxPPP and nucleotide metabolic dysfunction in lymphoma tumors.
AbstractList	Metabolic dysfunctions enabling increased nucleotide biosynthesis are necessary for supporting malignant proliferation. Our investigations indicate that upregulation of fatty acid synthase (FASN) and de novo lipogenesis, commonly observed in many cancers, are associated with nucleotide metabolic dysfunction in lymphoma. The results from our experiments showed that ribonucleotide and deoxyribonucleotide pool depletion, suppression of global RNA/DNA synthesis, and cell cycle inhibition occurred in the presence of FASN inhibition. Subsequently, we observed that FASN inhibition caused metabolic blockade in the rate-limiting step of the oxidative branch of the pentose phosphate pathway (oxPPP) catalyzed by phosphogluconate dehydrogenase (PGDH). Furthermore, we determined that FASN inhibitor treatment resulted in NADPH accumulation and inhibition of PGDH enzyme activity. NADPH is a cofactor utilized by FASN, also a known allosteric inhibitor of PGDH. Through cell-free enzyme assays consisting of FASN and PGDH, we delineated that the PGDH-catalyzed ribulose-5-phosphate synthesis is enhanced in the presence of FASN and is suppressed by increasing concentrations of NADPH. Additionally, we observed that FASN and PGDH were colocalized in the cytosol. The results from these experiments led us to conclude that NADP–NADPH turnover and the reciprocal stimulation of FASN and PGDH catalysis are involved in promoting oxPPP and nucleotide biosynthesis in lymphoma. Finally, a transcriptomic analysis of non-Hodgkin’s lymphoma (n = 624) revealed the increased expression of genes associated with metabolic functions interlinked with oxPPP, while the expression of genes participating in oxPPP remained unaltered. Together we conclude that FASN–PGDH enzymatic interactions are involved in enabling oxPPP and nucleotide metabolic dysfunction in lymphoma tumors. Metabolic dysfunctions enabling increased nucleotide biosynthesis are necessary for supporting malignant proliferation. Our investigations indicate that upregulation of fatty acid synthase (FASN) and de novo lipogenesis, commonly observed in many cancers, are associated with nucleotide metabolic dysfunction in lymphoma. The results from our experiments showed that ribonucleotide and deoxyribonucleotide pool depletion, suppression of global RNA/DNA synthesis, and cell cycle inhibition occurred in the presence of FASN inhibition. Subsequently, we observed that FASN inhibition caused metabolic blockade in the rate-limiting step of the oxidative branch of the pentose phosphate pathway (oxPPP) catalyzed by phosphogluconate dehydrogenase (PGDH). Furthermore, we determined that FASN inhibitor treatment resulted in NADPH accumulation and inhibition of PGDH enzyme activity. NADPH is a cofactor utilized by FASN, also a known allosteric inhibitor of PGDH. Through cell-free enzyme assays consisting of FASN and PGDH, we delineated that the PGDH-catalyzed ribulose-5-phosphate synthesis is enhanced in the presence of FASN and is suppressed by increasing concentrations of NADPH. Additionally, we observed that FASN and PGDH were colocalized in the cytosol. The results from these experiments led us to conclude that NADP–NADPH turnover and the reciprocal stimulation of FASN and PGDH catalysis are involved in promoting oxPPP and nucleotide biosynthesis in lymphoma. Finally, a transcriptomic analysis of non-Hodgkin’s lymphoma ( n = 624) revealed the increased expression of genes associated with metabolic functions interlinked with oxPPP, while the expression of genes participating in oxPPP remained unaltered. Together we conclude that FASN–PGDH enzymatic interactions are involved in enabling oxPPP and nucleotide metabolic dysfunction in lymphoma tumors. Metabolic dysfunctions enabling increased nucleotide biosynthesis are necessary for supporting malignant proliferation. Our investigations indicate that upregulation of fatty acid synthase (FASN) and de novo lipogenesis, commonly observed in many cancers, are associated with nucleotide metabolic dysfunction in lymphoma. The results from our experiments showed that ribonucleotide and deoxyribonucleotide pool depletion, suppression of global RNA/DNA synthesis, and cell cycle inhibition occurred in the presence of FASN inhibition. Subsequently, we observed that FASN inhibition caused metabolic blockade in the rate-limiting step of the oxidative branch of the pentose phosphate pathway (oxPPP) catalyzed by phosphogluconate dehydrogenase (PGDH). Furthermore, we determined that FASN inhibitor treatment resulted in NADPH accumulation and inhibition of PGDH enzyme activity. NADPH is a cofactor utilized by FASN, also a known allosteric inhibitor of PGDH. Through cell-free enzyme assays consisting of FASN and PGDH, we delineated that the PGDH-catalyzed ribulose-5-phosphate synthesis is enhanced in the presence of FASN and is suppressed by increasing concentrations of NADPH. Additionally, we observed that FASN and PGDH were colocalized in the cytosol. The results from these experiments led us to conclude that NADP-NADPH turnover and the reciprocal stimulation of FASN and PGDH catalysis are involved in promoting oxPPP and nucleotide biosynthesis in lymphoma. Finally, a transcriptomic analysis of non-Hodgkin's lymphoma (n = 624) revealed the increased expression of genes associated with metabolic functions interlinked with oxPPP, while the expression of genes participating in oxPPP remained unaltered. Together we conclude that FASN-PGDH enzymatic interactions are involved in enabling oxPPP and nucleotide metabolic dysfunction in lymphoma tumors.Metabolic dysfunctions enabling increased nucleotide biosynthesis are necessary for supporting malignant proliferation. Our investigations indicate that upregulation of fatty acid synthase (FASN) and de novo lipogenesis, commonly observed in many cancers, are associated with nucleotide metabolic dysfunction in lymphoma. The results from our experiments showed that ribonucleotide and deoxyribonucleotide pool depletion, suppression of global RNA/DNA synthesis, and cell cycle inhibition occurred in the presence of FASN inhibition. Subsequently, we observed that FASN inhibition caused metabolic blockade in the rate-limiting step of the oxidative branch of the pentose phosphate pathway (oxPPP) catalyzed by phosphogluconate dehydrogenase (PGDH). Furthermore, we determined that FASN inhibitor treatment resulted in NADPH accumulation and inhibition of PGDH enzyme activity. NADPH is a cofactor utilized by FASN, also a known allosteric inhibitor of PGDH. Through cell-free enzyme assays consisting of FASN and PGDH, we delineated that the PGDH-catalyzed ribulose-5-phosphate synthesis is enhanced in the presence of FASN and is suppressed by increasing concentrations of NADPH. Additionally, we observed that FASN and PGDH were colocalized in the cytosol. The results from these experiments led us to conclude that NADP-NADPH turnover and the reciprocal stimulation of FASN and PGDH catalysis are involved in promoting oxPPP and nucleotide biosynthesis in lymphoma. Finally, a transcriptomic analysis of non-Hodgkin's lymphoma (n = 624) revealed the increased expression of genes associated with metabolic functions interlinked with oxPPP, while the expression of genes participating in oxPPP remained unaltered. Together we conclude that FASN-PGDH enzymatic interactions are involved in enabling oxPPP and nucleotide metabolic dysfunction in lymphoma tumors.
Audience	PUBLIC
Author	Abermil, Nasséra Beheshti, Afshin Varshney, Rohan R. Chen, Ying Su, Xiaoyang Lansigan, Frederick Bijan, Mahboubi Evens, Andrew M. David, Kevin A. Kim, Baek Mokhtar, Maisarah Dolnikowski, Gregory G. Passero, Frank C. Ravi, Dashnamoorthy Matthan, Nirupa R. Dave, Sandeep S. Rudolph, Michael C. Kinlaw, William Puliti, Patrick
AuthorAffiliation	11 Metabolomics Core, Rutgers Cancer Institute of New Jersey , New Brunswick, NJ , United States 15 Center for Drug Discovery, Children’s Healthcare of Atlanta , Atlanta, GA , United States 1 Division of Blood Disorders, Rutgers Cancer Institute of New Jersey , New Brunswick, NJ , United States 6 Department of Medicine, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center , Lebanon, NH , United States 3 Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard , Cambridge, MA , United States 12 Bioinformatics Core, Rutgers Cancer Institute of New Jersey , New Brunswick, NJ , United States 2 Department of Medicine, Robert Wood Johnson Medical School, Rutgers University , New Brunswick, NJ , United States 14 Harold Hamm Diabetes Center, The University of Oklahoma Health Sciences Center , Oklahoma, OK , United States 10 Department of Medicine, University of Rochester Medical Center , Rochester, NY , United States 9 Jean Mayer United St
AuthorAffiliation_xml	– name: 4 KBR, Space Biosciences Division, National Aeronautical and Space Administration, Ames Research Center, Moffett Field , CA , United States – name: 13 Department of Pediatrics, School of Medicine, Emory University , Atlanta, GA , United States – name: 10 Department of Medicine, University of Rochester Medical Center , Rochester, NY , United States – name: 11 Metabolomics Core, Rutgers Cancer Institute of New Jersey , New Brunswick, NJ , United States – name: 9 Jean Mayer United States Department of Agriculture (USDA) Human Nutrition Research Center on Aging, Tufts University , Boston, MA , United States – name: 2 Department of Medicine, Robert Wood Johnson Medical School, Rutgers University , New Brunswick, NJ , United States – name: 8 Department of Medicine, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth , Lebanon, NH , United States – name: 15 Center for Drug Discovery, Children’s Healthcare of Atlanta , Atlanta, GA , United States – name: 16 Department of Medicine, Duke Cancer Institute, Duke University Medical Center , Durham, NC , United States – name: 7 Department of Medicine, Section of Endocrinology and Metabolism, Geisel School of Medicine at Dartmouth , Hanover, NH , United States – name: 3 Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard , Cambridge, MA , United States – name: 1 Division of Blood Disorders, Rutgers Cancer Institute of New Jersey , New Brunswick, NJ , United States – name: 5 Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Service d’Hématologie Biologique , Paris , France – name: 14 Harold Hamm Diabetes Center, The University of Oklahoma Health Sciences Center , Oklahoma, OK , United States – name: 6 Department of Medicine, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center , Lebanon, NH , United States – name: 12 Bioinformatics Core, Rutgers Cancer Institute of New Jersey , New Brunswick, NJ , United States
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Cites_doi	10.1111/brv.12140 10.1016/S0021-9258(18)64849-5 10.1016/j.ebiom.2015.06.020 10.1016/j.ebiom.2016.12.012 10.1016/j.cell.2017.09.027 10.1016/S0021-9258(19)70674-7 10.1093/nar/gkv047 10.4049/jimmunol.170.2.913 10.3390/cancers11050688 10.1158/0008-5472.CAN-18-2486 10.1021/acs.analchem.7b00396 10.1074/jbc.M114.551051 10.4137/CIN.S34144 10.1158/0008-5472.CAN-05-4673 10.1111/j.1365-2818.2006.01706.x 10.1016/j.ab.2012.06.013 10.14694/EdBook_AM.2015.35.e449 10.1172/JCI112412 10.1016/j.canlet.2014.02.019 10.1074/jbc.M508810200 10.1158/0008-5472.CAN-15-2477 10.1093/nar/gkv380 10.1517/17425247.4.5.513 10.1016/j.tibs.2014.06.005 10.1016/j.bbalip.2013.07.008 10.1093/bioinformatics/btw313 10.1016/j.gene.2017.09.005 10.1038/nrc2222 10.1007/BF00928361 10.2174/1570163812666150602144310 10.1073/pnas.1205299110 10.1016/S0022-2275(20)40190-7 10.1038/sj.bjc.6605007 10.1093/oxfordjournals.jbchem.a122739 10.1021/ac1021166 10.2217/fon.10.11 10.1074/jbc.M408573200 10.1002/ijc.24262 10.1093/nar/gky310 10.1074/jbc.273.9.4937 10.1007/s12308-012-0166-4 10.1080/10245330500141507 10.18632/oncotarget.6214
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Keywords	Lipid Metabolism Non-Hodgkin Lymphoma Nucleotides Fasn, Metabolomics Pentose Phosphate Pathway non-Hodgkin lymphoma metabolomics nucleotides FASN pentose phosphate pathway lipid metabolism
Language	English
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Notes	ARC Ames Research Center ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Sofia Avnet, University of Bologna, Italy; Aleš Dvořák, Charles University, Czechia This article was submitted to Cancer Metabolism, a section of the journal Frontiers in Oncology Edited by: Andrea Morandi, University of Florence, Italy
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References	Jing (B33) 2019; 79 Ventura (B15) 2015; 2 Flavin (B6) 2010; 6 Louie (B39) 2013; 1831 Fornalewicz (B32) 2017; 635 Rudolph (B30) 2012; 428 Diab (B36) 2007; 4 Frey (B4) 2006; 281 Heuer (B16) 2017; 16 Chong (B26) 2018; 46 Fragoso (B8) 2003; 170 Gu (B21) 2016; 32 Yoshii (B1) 2015; 356 Beheshti (B19) 2015; 6 Morrison (B23) 1964; 5 Vizan (B34) 2009; 124 Flaumenhaft (B7) 2005; 10 Melamud (B24) 2010; 82 Zhang (B10) 2013; 110 Patra (B37) 2014; 39 Stincone (B43) 2015; 90 Mashima (B2) 2009; 100 Rodwell (B3) 2018 Kuhajda (B5) 2006; 66 Ravi (B17) 2016; 76 Funabashi (B14) 1989; 105 Diamond (B28) 2004; 279 Traut (B38) 1994; 140 Su (B25) 2017; 89 Lane (B45) 2015; 43 Roth (B44) 1986; 77 Xia (B27) 2015; 43 Dufort (B41) 2014; 289 Baudino (B13) 2015; 12 Danilova (B11) 2013; 6 Bolte (B29) 2006; 224 Joshi (B31) 1998; 273 Villa (B35) 2019; 11 Folch (B22) 1957; 226 Meisenberg (B40) 2017 Reitzer (B42) 1980; 255 Menendez (B9) 2007; 7 Beheshti (B18) 2015; 14 Nowakowski (B12) 2015 Reddy (B20) 2017; 171
References_xml	– volume: 90 year: 2015 ident: B43 article-title: The Return of Metabolism: Biochemistry and Physiology of the Pentose Phosphate Pathway publication-title: Biol Rev Camb Philos Soc doi: 10.1111/brv.12140 – volume: 226 start-page: 497 year: 1957 ident: B22 article-title: A Simple Method for the Isolation and Purification of Total Lipides From Animal Tissues publication-title: J Biol Chem doi: 10.1016/S0021-9258(18)64849-5 – volume: 2 year: 2015 ident: B15 article-title: Inhibition of De Novo Palmitate Synthesis by Fatty Acid Synthase Induces Apoptosis in Tumor Cells by Remodeling Cell Membranes, Inhibiting Signaling Pathways, and Reprogramming Gene Expression publication-title: EBioMedicine doi: 10.1016/j.ebiom.2015.06.020 – volume: 16 start-page: 51 year: 2017 ident: B16 article-title: FASN Inhibition and Taxane Treatment Combine to Enhance Anti-Tumor Efficacy in Diverse Xenograft Tumor Models Through Disruption of Tubulin Palmitoylation and Microtubule Organization and FASN Inhibition-Mediated Effects on Oncogenic Signaling and Gene Expression publication-title: EBioMedicine doi: 10.1016/j.ebiom.2016.12.012 – volume: 171 start-page: 481 year: 2017 ident: B20 article-title: Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma publication-title: Cell doi: 10.1016/j.cell.2017.09.027 – start-page: 617 volume-title: Principles of Medical Biochemistry year: 2017 ident: B40 – volume: 255 year: 1980 ident: B42 article-title: The Pentose Cycle. Control and Essential Function in HeLa Cell Nucleic Acid Synthesis publication-title: J Biol Chem doi: 10.1016/S0021-9258(19)70674-7 – volume: 43 year: 2015 ident: B45 article-title: Regulation of Mammalian Nucleotide Metabolism and Biosynthesis publication-title: Nucleic Acids Res doi: 10.1093/nar/gkv047 – volume: 170 year: 2003 ident: B8 article-title: Lipid Raft Distribution of CD4 Depends on its Palmitoylation and Association With Lck, and Evidence for CD4-Induced Lipid Raft Aggregation as an Additional Mechanism to Enhance CD3 Signaling publication-title: J Immunol doi: 10.4049/jimmunol.170.2.913 – volume: 11 year: 2019 ident: B35 article-title: Cancer Cells Tune the Signaling Pathways to Empower De Novo Synthesis of Nucleotides publication-title: Cancers (Basel) doi: 10.3390/cancers11050688 – volume: 79 year: 2019 ident: B33 article-title: Cell-Cycle-Dependent Phosphorylation of PRPS1 Fuels Nucleotide Synthesis and Promotes Tumorigenesis publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-18-2486 – volume: 89 year: 2017 ident: B25 article-title: Metabolite Spectral Accuracy on Orbitraps publication-title: Anal Chem doi: 10.1021/acs.analchem.7b00396 – volume: 289 year: 2014 ident: B41 article-title: Glucose-Dependent De Novo Lipogenesis in B Lymphocytes: A Requirement for Atp-Citrate Lyase in Lipopolysaccharide-Induced Differentiation publication-title: J Biol Chem doi: 10.1074/jbc.M114.551051 – volume: 14 year: 2015 ident: B18 article-title: The Impact of Age and Sex in DLBCL: Systems Biology Analyses Identify Distinct Molecular Changes and Signaling Networks publication-title: Cancer Inform doi: 10.4137/CIN.S34144 – volume: 66 year: 2006 ident: B5 article-title: Fatty Acid Synthase and Cancer: New Application of an Old Pathway publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-05-4673 – volume: 224 year: 2006 ident: B29 article-title: A Guided Tour Into Subcellular Colocalization Analysis in Light Microscopy publication-title: J Microsc doi: 10.1111/j.1365-2818.2006.01706.x – volume: 428 year: 2012 ident: B30 article-title: Mammalian Fatty Acid Synthase Activity From Crude Tissue Lysates Tracing (1)(3)C-Labeled Substrates Using Gas Chromatography-Mass Spectrometry publication-title: Anal Biochem doi: 10.1016/j.ab.2012.06.013 – volume-title: Am Soc Clin Oncol Educ Book year: 2015 ident: B12 article-title: ABC, GCB, and Double-Hit Diffuse Large B-Cell Lymphoma: Does Subtype Make a Difference in Therapy Selection doi: 10.14694/EdBook_AM.2015.35.e449 – volume: 77 year: 1986 ident: B44 article-title: Ribose Metabolism and Nucleic Acid Synthesis in Normal and Glucose-6-Phosphate Dehydrogenase-Deficient Human Erythrocytes Infected With Plasmodium Falciparum publication-title: J Clin Invest doi: 10.1172/JCI112412 – volume: 356 year: 2015 ident: B1 article-title: Acetate/acetyl-CoA Metabolism Associated With Cancer Fatty Acid Synthesis: Overview and Application publication-title: Cancer Lett doi: 10.1016/j.canlet.2014.02.019 – volume: 281 year: 2006 ident: B4 article-title: Phosphatidylinositol 3-Kinase Gamma Signaling Through Protein Kinase Czeta Induces NADPH Oxidase-Mediated Oxidant Generation and NF-kappaB Activation in Endothelial Cells publication-title: J Biol Chem doi: 10.1074/jbc.M508810200 – volume: 76 year: 2016 ident: B17 article-title: Proteasomal Inhibition by Ixazomib Induces CHK1 and MYC-Dependent Cell Death in T-Cell and Hodgkin Lymphoma publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-15-2477 – volume: 43 year: 2015 ident: B27 article-title: MetaboAnalyst 3.0–Making Metabolomics More Meaningful publication-title: Nucleic Acids Res doi: 10.1093/nar/gkv380 – volume: 4 year: 2007 ident: B36 article-title: Nucleoside Analogue Delivery Systems in Cancer Therapy publication-title: Expert Opin Drug Deliv doi: 10.1517/17425247.4.5.513 – volume-title: Harper’s Illustrated Biochemistry. year: 2018 ident: B3 – volume: 39 year: 2014 ident: B37 article-title: The Pentose Phosphate Pathway and Cancer publication-title: Trends Biochem Sci doi: 10.1016/j.tibs.2014.06.005 – volume: 1831 year: 2013 ident: B39 article-title: Cancer Cells Incorporate and Remodel Exogenous Palmitate Into Structural and Oncogenic Signaling Lipids publication-title: Biochim Biophys Acta doi: 10.1016/j.bbalip.2013.07.008 – volume: 32 year: 2016 ident: B21 article-title: Complex Heatmaps Reveal Patterns and Correlations in Multidimensional Genomic Data publication-title: Bioinformatics doi: 10.1093/bioinformatics/btw313 – volume: 635 year: 2017 ident: B32 article-title: Silencing of the Pentose Phosphate Pathway Genes Influences DNA Replication in Human Fibroblasts publication-title: Gene doi: 10.1016/j.gene.2017.09.005 – volume: 7 year: 2007 ident: B9 article-title: Fatty Acid Synthase and the Lipogenic Phenotype in Cancer Pathogenesis publication-title: Nat Rev Cancer doi: 10.1038/nrc2222 – volume: 140 start-page: 1 year: 1994 ident: B38 article-title: Physiological Concentrations of Purines and Pyrimidines publication-title: Mol Cell Biochem doi: 10.1007/BF00928361 – volume: 12 start-page: 3 year: 2015 ident: B13 article-title: Targeted Cancer Therapy: The Next Generation of Cancer Treatment publication-title: Curr Drug Discovery Technol doi: 10.2174/1570163812666150602144310 – volume: 110 year: 2013 ident: B10 article-title: Genetic Heterogeneity of Diffuse Large B-Cell Lymphoma publication-title: Proc Natl Acad Sci USA doi: 10.1073/pnas.1205299110 – volume: 5 year: 1964 ident: B23 article-title: Preparation of Fatty Acid Methyl Esters and Dimethylacetals From Lipids With Boron Fluoride–Methanol publication-title: J Lipid Res doi: 10.1016/S0022-2275(20)40190-7 – volume: 100 year: 2009 ident: B2 article-title: De Novo Fatty-Acid Synthesis and Related Pathways as Molecular Targets for Cancer Therapy publication-title: Br J Cancer doi: 10.1038/sj.bjc.6605007 – volume: 105 year: 1989 ident: B14 article-title: Binding Site of Cerulenin in Fatty Acid Synthetase publication-title: J Biochem doi: 10.1093/oxfordjournals.jbchem.a122739 – volume: 82 year: 2010 ident: B24 article-title: Metabolomic Analysis and Visualization Engine for LC-MS Data publication-title: Anal Chem doi: 10.1021/ac1021166 – volume: 6 year: 2010 ident: B6 article-title: Fatty Acid Synthase as a Potential Therapeutic Target in Cancer publication-title: Future Oncol doi: 10.2217/fon.10.11 – volume: 279 year: 2004 ident: B28 article-title: Macrophage Tropism of HIV-1 Depends on Efficient Cellular dNTP Utilization by Reverse Transcriptase publication-title: J Biol Chem doi: 10.1074/jbc.M408573200 – volume: 124 year: 2009 ident: B34 article-title: Modulation of Pentose Phosphate Pathway During Cell Cycle Progression in Human Colon Adenocarcinoma Cell Line HT29 publication-title: Int J Cancer doi: 10.1002/ijc.24262 – volume: 46 year: 2018 ident: B26 article-title: MetaboAnalyst 4.0: Towards More Transparent and Integrative Metabolomics Analysis publication-title: Nucleic Acids Res doi: 10.1093/nar/gky310 – volume: 273 year: 1998 ident: B31 article-title: Differential Affinity Labeling of the Two Subunits of the Homodimeric Animal Fatty Acid Synthase Allows Isolation of Heterodimers Consisting of Subunits That Have Been Independently Modified publication-title: J Biol Chem doi: 10.1074/jbc.273.9.4937 – volume: 6 year: 2013 ident: B11 article-title: FASN and CD36 Predict Survival in Rituximab-Treated Diffuse Large B-Cell Lymphoma publication-title: J Hematop doi: 10.1007/s12308-012-0166-4 – volume: 10 year: 2005 ident: B7 article-title: Protein Palmitoylation in Signal Transduction of Hematopoietic Cells publication-title: Hematology doi: 10.1080/10245330500141507 – volume: 6 year: 2015 ident: B19 article-title: Tumor-Host Signaling Interaction Reveals a Systemic, Age-Dependent Splenic Immune Influence on Tumor Development publication-title: Oncotarget doi: 10.18632/oncotarget.6214
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Snippet	Metabolic dysfunctions enabling increased nucleotide biosynthesis are necessary for supporting malignant proliferation. Our investigations indicate that...
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SubjectTerms	Aerospace Medicine FASN Human health and pathology Life Sciences lipid metabolism metabolomics non-Hodgkin lymphoma nucleotides Oncology pentose phosphate pathway
Title	Oncogenic Integration of Nucleotide Metabolism via Fatty Acid Synthase in Non-Hodgkin Lymphoma
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