{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T17:20:27Z","timestamp":1763400027345,"version":"build-2065373602"},"reference-count":155,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (19K22658; 20H00541; 21K19526; AMED, Japan; 17cm0106414h0002) to H.I. Partial support was received from Princ","award":["This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (19K22658; 20H00541; 21K19526; AMED, Japan; 17cm0106414h0002) to H.I. Partial support was received from Princ"],"award-info":[{"award-number":["This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (19K22658; 20H00541; 21K19526; AMED, Japan; 17cm0106414h0002) to H.I. Partial support was received from Princ"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>As cancer is a genetic disease, methylation defines a biologically malignant phenotype of cancer in the association of one-carbon metabolism-dependent S-adenosylmethionine (SAM) as a methyl donor in each cell. Methylated substances are involved in intracellular metabolism, but via intercellular communication, some of these can also be secreted to affect other substances. Although metabolic analysis at the single-cell level remains challenging, studying the \u201cmethylosystem\u201d (i.e., the intercellular and intracellular communications of upstream regulatory factors and\/or downstream effectors that affect the epigenetic mechanism involving the transfer of a methyl group from SAM onto the specific positions of nucleotides or other metabolites in the tumor microenvironment) and tracking these metabolic products are important research tasks for understanding spatial heterogeneity. Here, we discuss and highlight the involvement of RNA and nicotinamide, recently emerged targets, in SAM-producing one-carbon metabolism in cancer cells, cancer-associated fibroblasts, and immune cells. Their significance and implications will contribute to the discovery of efficient methods for the diagnosis of and therapeutic approaches to human cancer.<\/jats:p>","DOI":"10.3390\/cancers13205088","type":"journal-article","created":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T08:09:32Z","timestamp":1634026172000},"page":"5088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Methylosystem for Cancer Sieging Strategy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7504-859X","authenticated-orcid":false,"given":"Shotaro","family":"Tatekawa","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Yamadaoka 2-2, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Ofusa","sequence":"additional","affiliation":[{"name":"Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Yamadaoka 2-2, Osaka 565-0871, Japan"},{"name":"Food and Life-Science Laboratory, Prophoenix Division, Idea Consultants, Inc., Osaka 559-8519, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3125-4818","authenticated-orcid":false,"given":"Ryota","family":"Chijimatsu","sequence":"additional","affiliation":[{"name":"Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Yamadaoka 2-2, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5497-6856","authenticated-orcid":false,"given":"Andrea","family":"Vecchione","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, University of Rome \u201cSapienza\u201d, Santo Andrea Hospital, Via di Grottarossa, 1035-00189 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Tamari","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Yamadaoka 2-2, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Yamadaoka 2-2, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideshi","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Yamadaoka 2-2, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gorchs, L., and Kaipe, H. (2021). Interactions between Cancer-Associated Fibroblasts and T Cells in the Pancreatic Tumor Microenvironment and the Role of Chemokines. Cancers, 13.","DOI":"10.3390\/cancers13122995"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41568-021-00383-9","article-title":"The immunological and metabolic landscape in primary and metastatic liver cancer","volume":"21","author":"Li","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Moindjie, H., Rodrigues-Ferreira, S., and Nahmias, C. (2021). Mitochondrial Metabolism in Carcinogenesis and Cancer Therapy. Cancers, 13.","DOI":"10.3390\/cancers13133311"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Takeda, Y., Chijimatsu, R., Vecchione, A., Arai, T., Kitagawa, T., Ofusa, K., Yabumoto, M., Hirotsu, T., Eguchi, H., and Doki, Y. (2021). Impact of One-Carbon Metabolism-Driving Epitranscriptome as a Therapeutic Target for Gastrointestinal Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147278"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.1038\/s41467-021-24861-8","article-title":"An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites","volume":"12","author":"Papadimitriou","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1158\/1055-9965.EPI-15-0594","article-title":"Dietary Intake of One-Carbon Metabolism-Related Nutrients and Pancreatic Cancer Risk: The Singapore Chinese Health Study","volume":"25","author":"Huang","year":"2016","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s13668-018-0237-y","article-title":"Folate and its impact on cancer risk","volume":"7","author":"Pieroth","year":"2018","journal-title":"Curr. Nutr. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kitakaze, M., Chijimatsu, R., Vecchione, A., Kitagawa, T., Doki, Y., Eguchi, H., and Ishii, H. (2021). Epithelial Cell Transformation and Senescence as Indicators of Genome Aging: Current Advances and Unanswered Questions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147544"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s41232-021-00170-x","article-title":"Single-cell and spatial analyses of cancer cells: Toward elucidating the molecular mechanisms of clonal evolution and drug resistance acquisition","volume":"41","author":"Nagasawa","year":"2021","journal-title":"Inflamm. Regen."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10462","DOI":"10.1021\/acs.analchem.1c00106","article-title":"Single Cell Metabolite Detection Using Inertial Microfluidics-Assisted Ion Mobility Mass Spectrometry","volume":"93","author":"Zhang","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.apsb.2020.08.011","article-title":"Diversity of the reaction mechanisms of SAM-dependent enzymes","volume":"11","author":"Sun","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lauinger, L., and Kaiser, P. (2021). Sensing and Signaling of Methionine Metabolism. Metabolites, 11.","DOI":"10.3390\/metabo11020083"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the origin of cancer cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation","volume":"324","author":"Thompson","year":"2009","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6479","DOI":"10.1158\/1078-0432.CCR-09-0889","article-title":"MYC-induced cancer cell energy metabolism and therapeutic opportunities","volume":"15","author":"Dang","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kim, S.-H., and Baek, K.-H. (2021). Regulation of Cancer Metabolism by Deubiquitinating Enzymes: The Warburg Effect. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126173"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19611","DOI":"10.1073\/pnas.1117773108","article-title":"Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of \u03b1-ketoglutarate to citrate to support cell growth and viability","volume":"108","author":"Wise","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature10602","article-title":"Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia","volume":"481","author":"Metallo","year":"2011","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"36289","DOI":"10.1038\/srep36289","article-title":"Oncometabolite D-2-Hydroxyglurate Directly Induces Epithelial-Mesenchymal Transition and is Associated with Distant Metastasis in Colorectal Cancer","volume":"6","author":"Colvin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.3892\/ijo.2015.2833","article-title":"Mathematical analysis predicts imbalanced IDH1\/2 expression associates with 2-HG-inactivating \u03b2-oxygenation pathway in colorectal cancer","volume":"46","author":"Koseki","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature12040","article-title":"Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway","volume":"496","author":"Son","year":"2013","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"38415","DOI":"10.1038\/srep38415","article-title":"Metabolic Adaptation to Nutritional Stress in Human Colorectal Cancer","volume":"6","author":"Miyo","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18949","DOI":"10.1038\/srep18949","article-title":"BRAFV600E inhibition stimulates AMP-activated protein kinase-mediated autophagy in colorectal cancer cells","volume":"6","author":"Sueda","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100923","DOI":"10.1016\/j.mam.2020.100923","article-title":"Immunometabolic control of hematopoiesis","volume":"77","author":"Hajishengallis","year":"2021","journal-title":"Mol. Aspects Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"One-Carbon Metabolism in Health and Disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/j.1365-2141.2006.06119.x","article-title":"A tribute to Sidney Farber\u2014The father of modern chemotherapy","volume":"134","author":"Miller","year":"2006","journal-title":"Br. J. Haematol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bedoui, Y., Guillot, X., S\u00e9lambarom, J., Guiraud, P., Giry, C., Jaffar-Bandjee, M.C., Ralandison, S., and Gasque, P. (2019). Methotrexate an Old Drug with New Tricks. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205023"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41598-017-18456-x","article-title":"Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis","volume":"8","author":"Koseki","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e01021","DOI":"10.1016\/j.heliyon.2018.e01021","article-title":"Drug discovery of anticancer drugs targeting methylenetetrahydrofolate dehydrogenase 2","volume":"4","author":"Asai","year":"2018","journal-title":"Heliyon"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.canlet.2019.11.023","article-title":"One-carbon metabolism for cancer diagnostic and therapeutic approaches","volume":"470","author":"Asai","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kaiser, P. (2020). Methionine Dependence of Cancer. Biomolecules, 10.","DOI":"10.3390\/biom10040568"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/jcp.1041190106","article-title":"Altered methionine metabolism occurs in all members of a set of diverse human tumor cell lines","volume":"119","author":"Stern","year":"1984","journal-title":"J. Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.4161\/cc.22767","article-title":"Downregulation of Cdc6 and pre-replication complexes in response to methionine stress in breast cancer cells","volume":"11","author":"Booher","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40170-016-0148-6","article-title":"Metabolic changes associated with methionine stress sensitivity in MDA-MB-468 breast cancer cells","volume":"4","author":"Borrego","year":"2016","journal-title":"Cancer Metab."},{"key":"ref_35","first-page":"50","article-title":"S-adenosylmethionine limitation induces p38 mitogen-activated protein kinase and triggers cell cycle arrest in G1","volume":"127","author":"Lin","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/0003-9861(59)90225-5","article-title":"Quantitative nutritional studies with water-soluble, chemically defined diets. VIII. The forced feeding of diets each lacking in one essential amino acid","volume":"81","author":"Sugimura","year":"1959","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1128\/MCB.22.12.4158-4166.2002","article-title":"Mitochondrial NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase is essential for embryonic development","volume":"22","author":"Pietro","year":"2002","journal-title":"Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.cmet.2016.06.007","article-title":"Mitochondrial biogenesis and proteome remodeling promote one-carbon metabolism for T cell activation","volume":"24","author":"Santos","year":"2016","journal-title":"Cell Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/j.cmet.2016.04.016","article-title":"Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway","volume":"23","author":"Ducker","year":"2016","journal-title":"Cell Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1126\/science.aag3145","article-title":"Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation","volume":"354","author":"Taya","year":"2016","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1126\/science.103.2682.646","article-title":"Granulocytopenia and Anemia in Rats Fed Diets of Low Casein Content","volume":"103","author":"Kornberg","year":"1946","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0021-9258(18)43060-8","article-title":"Amino acids in the production of granulocytes in rats","volume":"64","author":"Kornberg","year":"1946","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41586-019-1244-x","article-title":"Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation","volume":"571","author":"Wilkinson","year":"2019","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.3892\/ijo.2014.2671","article-title":"Identification of chemoradiation-resistant osteosarcoma stem cells using an imaging system for proteasome activity","volume":"45","author":"Tamari","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.3892\/ijo.2014.2670","article-title":"Visualization and characterization of cancer stem-like cells in cervical cancer","volume":"45","author":"Hayashi","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.3892\/or.2013.2952","article-title":"Novel drug discovery system for cancer stem cells in human squamous cell carcinoma of the esophagus","volume":"31","author":"Kano","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41420-018-0117-7","article-title":"Polyamine flux suppresses histone lysine demethylases and enhances ID1 expression in cancer stem cells","volume":"4","author":"Tamari","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.ajhg.2021.06.015","article-title":"Anatomy of DNA methylation signatures: Emerging insights and applications","volume":"108","author":"Goodman","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Adashek, J.J., Janku, F., and Kurzrock, R. (2021). Signed in Blood: Circulating Tumor DNA in Cancer Diagnosis, Treatment and Screening. Cancers, 13.","DOI":"10.3390\/cancers13143600"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1111\/cas.14095","article-title":"Significant epitranscriptomes in heterogeneous cancer","volume":"110","author":"Konno","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3888","DOI":"10.1038\/s41467-019-11826-1","article-title":"Distinct methylation levels of mature microRNAs in gastrointestinal cancers","volume":"10","author":"Konno","year":"2019","journal-title":"Nat. Commun"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nchembio.1432","article-title":"A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation","volume":"10","author":"Liu","year":"2014","journal-title":"Nat. Chem. Biol"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1146\/annurev-cellbio-100616-060758","article-title":"Rethinking m6A Readers, Writers, and Erasers","volume":"33","author":"Meyer","year":"2017","journal-title":"Annu Rev. Cell Dev. Biol"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nchembio.687","article-title":"He CN6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated, FTO","volume":"7","author":"Jia","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.molcel.2012.10.015","article-title":"ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility","volume":"49","author":"Zheng","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7476","DOI":"10.18632\/oncotarget.23554","article-title":"Oncogene c-Myc Promotes Epitranscriptome m6A Reader YTHDF1 Expression in Colorectal Cancer","volume":"9","author":"Nishizawa","year":"2017","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0021-9258(18)56110-X","article-title":"Methylation of nicotinamide with soluble enzyme system from rat liver","volume":"189","author":"Cantoni","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.1021\/ja01131a519","article-title":"The nature of the active methyl donor formed enzymatically from L-methionine and adenosinetriphosphate","volume":"74","author":"Cantoni","year":"1952","journal-title":"J. Am. Chem. Soc."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kujund\u017ei\u0107, R.N., Prpi\u0107m \u0110akovi\u0107, N., Dabeli\u0107, N., Tomljanovi\u0107, M., Mojze\u0161, A., Fr\u00f6be, A., and Tro\u0161elj, K.G. (2021). Nicotinamide N-Methyltransferase in Acquisition of Stem Cell Properties and Therapy Resistance in Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115681"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.tem.2017.02.004","article-title":"Nicotinamide methyltransferase: More than a vitamin B3 clearance enzyme","volume":"28","author":"Pissios","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1177\/1178646917691739","article-title":"Nicotinamide N-methyltransferase in health and cancer","volume":"10","author":"Ramsden","year":"2017","journal-title":"Int. J. Tryptophan. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"656","DOI":"10.4149\/neo_2018_171024N680","article-title":"Nicotinamide N-methyltransferase as a potential marker for cancer","volume":"65","author":"Lu","year":"2018","journal-title":"Neoplasma"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.3389\/fphys.2018.01407","article-title":"Prognostic Value of Nicotinamide N-Methyltransferase Expression in Patients With Solid Tumors: A Systematic Review and Meta-Analysis","volume":"9","author":"Li","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1159\/000475432","article-title":"Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced Histone H3 Lysine9 Dimethylation in BEAS-2B Cells","volume":"41","author":"Li","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"26200","DOI":"10.18632\/oncotarget.15429","article-title":"Glucose deprivation elicits phenotypic plasticity via ZEB1-mediated expression of NNMT","volume":"8","author":"Kanska","year":"2017","journal-title":"Oncotarget"},{"key":"ref_66","first-page":"4592","article-title":"Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-beta1 expression","volume":"15","author":"Liang","year":"2018","journal-title":"Oncol. Lett"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11010-019-03573-0","article-title":"Downregulation of nicotinamide N-methyltransferase inhibits migration and epithelial-mesenchymal transition of esophageal squamous cell carcinoma via Wnt\/beta-catenin pathway","volume":"460","author":"Cui","year":"2019","journal-title":"Mol. Cell Biochem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1002\/mc.23209","article-title":"Nicotinamide N-methyltransferase decreases 5-fluorouracil sensitivity in human esophageal squamous cell carcinoma through metabolic reprogramming and promoting the Warburg effect","volume":"59","author":"Cui","year":"2020","journal-title":"Mol. Carcinog."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"45837","DOI":"10.18632\/oncotarget.9962","article-title":"Nicotinamide N-methyltransferase enhances resistance to 5-fluorouracil in colorectal cancer cells through inhibition of the ASK1-p38 MAPK pathway","volume":"7","author":"Xie","year":"2016","journal-title":"Oncotarget"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.1007\/s13277-013-0980-z","article-title":"Nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma","volume":"34","author":"Win","year":"2013","journal-title":"Tumour Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1002\/1878-0261.12544","article-title":"Elevated N-methyltransferase expression induced by hepatic stellate cells contributes to the metastasis of hepatocellular carcinoma via regulation of the CD44v3 isoform","volume":"13","author":"Li","year":"2019","journal-title":"Mol. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"eabe1174","DOI":"10.1126\/sciadv.abe1174","article-title":"1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer","volume":"7","author":"Kilgour","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"563","DOI":"10.2967\/jnumed.119.233122","article-title":"Theranostics Targeting Fibroblast Activation Protein in the Tumor Stroma: 64 Cu- and 225 Ac-Labeled FAPI-04 in Pancreatic Cancer Xenograft Mouse Models","volume":"61","author":"Watabe","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"693640","DOI":"10.3389\/fonc.2021.693640","article-title":"68Ga-FAPI-04 Versus 18F-FDG PET\/CT in the Detection of Hepatocellular Carcinoma","volume":"11","author":"Wang","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"R\u00f6hrich, M., Leitz, D., Glatting, F.M., Wefers, A.K., Weinheimer, O., Flechsig, P., Kahn, N., Mall, M.A., Giesel, F.L., and Kratochwil, C. (2021). Fibroblast Activation Protein specific PET\/CT imaging in fibrotic interstitial lung diseases and lung cancer: A translational exploratory study. J. Nucl. Med., 62.","DOI":"10.2967\/jnumed.121.261925"},{"key":"ref_76","first-page":"9195","article-title":"Nicotinamide N-methyltransferase enhances the progression of prostate cancer by stabilizing sirtuin 1","volume":"15","author":"You","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.bbrc.2015.10.023","article-title":"Nicotinamide N-methyltransferase increases complex I activity in SH-SY5Y cells via sirtuin 3","volume":"467","author":"Liu","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Campagna, R., Salvolini, E., Pompei, V., Pozzi, V., Salvucci, A., Molinelli, E., Brisigotti, V., Sartini, D., Campanati, A., and Offidani, A. (2021). Nicotinamide N-methyltransferase gene silencing enhances chemosensitivity of melanoma cell lines. Pigment. Cell Melanoma Res.","DOI":"10.1111\/pcmr.12993"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3892\/or.2021.8061","article-title":"Vanillin downregulates NNMT and attenuates NNMT-related resistance to 5-fluorouracil via ROS-induced cell apoptosis in colorectal cancer cells","volume":"45","author":"Li","year":"2021","journal-title":"Oncol Rep."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Akar, S., Duran, T., Azzawri, A.A., Ko\u00e7ak, N., \u00c7elik, \u00c7., and Y\u0131ld\u0131r\u0131m, H.\u0130. (2021). Small molecule inhibitor of nicotinamide N-methyltransferase shows anti-proliferative activity in HeLa cells. J. Obestet. Gynaecol., 1\u20139.","DOI":"10.1080\/01443615.2020.1854696"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/kjm2.12334","article-title":"Exosomal NNMT from peritoneum lavage fluid promotes peritoneal metastasis in gastric cancer","volume":"37","author":"Zhu","year":"2021","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Li, J., Yue, H., Yu, H., Lu, X., and Xue, X. (2021). Patients with low nicotinamide N-methyltransferase expression benefit significantly from bevacizumab treatment in ovarian cancer. BMC Cancer., 21.","DOI":"10.1186\/s12885-021-07785-w"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1369\/0022155420976590","article-title":"Accumulation of Nicotinamide N-Methyltransferase (NNMT) in Cancer-associated Fibroblasts: A Potential Prognostic and Predictive Biomarker for Gastric Carcinoma","volume":"69","author":"Zhang","year":"2021","journal-title":"J. Histochem Cytochem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1010428320977124","DOI":"10.1177\/1010428320977124","article-title":"Hepatoblastomas exhibit marked NNMT downregulation driven by promoter DNA hypermethylation","volume":"42","author":"Rivas","year":"2020","journal-title":"Tumour Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"580299","DOI":"10.3389\/fgene.2020.580299","article-title":"Nicotinamide N-Methyltransferase Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric Cancer","volume":"11","author":"Wu","year":"2020","journal-title":"Front. Genet."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s12935-020-01279-8","article-title":"Nicotinamide N-methyltransferase inhibits autophagy induced by oxidative stress through suppressing the AMPK pathway in breast cancer cells","volume":"20","author":"Yu","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1080\/01443615.2020.1732891","article-title":"Nicotinamide N-methyltransferase overexpression may be associated with poor prognosis in ovarian cancer","volume":"41","author":"Harmankaya","year":"2021","journal-title":"J. Obs. Gynaecol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1002\/iub.2265","article-title":"Cancer stem cell enrichment is associated with enhancement of nicotinamide N-methyltransferase expression","volume":"72","author":"Pozzi","year":"2020","journal-title":"IUBMB Life."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1002\/cam4.2890","article-title":"High stromal nicotinamide N-methyltransferase (NNMT) indicates poor prognosis in colorectal cancer","volume":"9","author":"Song","year":"2020","journal-title":"Cancer Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.3906\/sag-1907-166","article-title":"Nicotinamide N-methyltransferase expression and its association with phospho-Akt, p53 expression, and survival in high-grade endometrial cancer","volume":"49","author":"Akar","year":"2019","journal-title":"Turk. J. Med. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e13175","DOI":"10.1111\/eci.13175","article-title":"Nicotinamide N-methyltransferase in nonmelanoma skin cancers","volume":"49","author":"Pompei","year":"2019","journal-title":"Eur. J. Clin. Invest."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5427","DOI":"10.21873\/anticanres.13736","article-title":"Nicotinamide N-Methyltransferase and Its Precursor Substrate Methionine Directly and Indirectly Control Malignant Metabolism During Progression of Renal Cell Carcinoma","volume":"39","author":"Holstein","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_93","first-page":"1805","article-title":"Nicotinamide N-methyltransferase induces the proliferation and invasion of squamous cell carcinoma cells","volume":"42","author":"Hah","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13058-019-1150-z","article-title":"Nicotinamide N-methyltransferase enhances chemoresistance in breast cancer through SIRT1 protein stabilization","volume":"21","author":"Wang","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/s41586-019-1173-8","article-title":"Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts","volume":"569","author":"Eckert","year":"2019","journal-title":"Nature."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/PGP.0000000000000605","article-title":"Expression and Clinical Significance of Nicotinamide N-Methyltransferase in Cervical Squamous Cell Carcinoma","volume":"39","author":"Akar","year":"2020","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1097\/CMR.0000000000000548","article-title":"Analysis of nicotinamide N-methyltransferase in oral malignant melanoma and potential prognostic significance","volume":"29","author":"Mascitti","year":"2019","journal-title":"Melanoma Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.omtn.2018.03.011","article-title":"Targeting Nicotinamide N-Methyltransferase and miR-449a in EGFR-TKI-Resistant Non-Small-Cell Lung Cancer Cells","volume":"11","author":"Bach","year":"2018","journal-title":"Mol. Nucleic Acids."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Ganzetti, G., Sartini, D., Campanati, A., Rubini, C., Molinelli, E., Brisigotti, V., Cecati, M., Pozzi, V., Campagna, R., and Offidani, A. Nicotinamide N-methyltransferase: Potential involvement in cutaneous malignant melanoma. Melanoma Res., 2018 28, 82\u201388.","DOI":"10.1097\/CMR.0000000000000430"},{"key":"ref_100","first-page":"187","article-title":"Deregulation of Nicotinamide N-Methyltransferase and Gap Junction Protein Alpha-1 Causes Metastasis in Adenoid Cystic Carcinoma","volume":"38","author":"Ishibashi","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_101","first-page":"649","article-title":"Nicotinamide N-methyltransferase: A potential biomarker for worse prognosis in gastric carcinoma","volume":"6","author":"Chen","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Neely, B.A., Wilkins, C.E., Marlow, L.A., Malyarenko, D., Kim, Y., Ignatchenko, A., Sasinowska, H., Sasinowski, M., Nyalwidhe, J.O., and Kislinger, T. (2016). Proteotranscriptomic Analysis Reveals Stage Specific Changes in the Molecular Landscape of Clear-Cell Renal Cell Carcinoma. PLoS ONE., 11.","DOI":"10.1371\/journal.pone.0154074"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"19975","DOI":"10.18632\/oncotarget.7891","article-title":"Expression profile and prognostic value of NNMT in patients with pancreatic cancer","volume":"7","author":"Xu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Zhang, J., Wang, Y., Li, G., Yu, H., and Xie, X. (2014). Down-regulation of nicotinamide N-methyltransferase induces apoptosis in human breast cancer cells via the mitochondria-mediated pathway. PLoS ONE., 9.","DOI":"10.1371\/journal.pone.0089202"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Pozzi, V., Sartini, D., Morganti, S., Giuliante, R., Di Ruscio, G., Santarelli, A., Rocchetti, R., Rubini, C., Tomasetti, M., and Giannatempo, G. (2013). RNA-mediated gene silencing of nicotinamide N-methyltransferase is associated with decreased tumorigenicity in human oral carcinoma cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071272"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s12013-012-9451-1","article-title":"Upregulation of tissue and urinary nicotinamide N-methyltransferase in bladder cancer: Potential for the development of a urine-based diagnostic test","volume":"65","author":"Sartini","year":"2013","journal-title":"Cell Biochem. Biophys."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1515\/hsz-2012-0112","article-title":"Analysis of tissue and salivary nicotinamide N-methyltransferase in oral squamous cell carcinoma: Basis for the development of a noninvasive diagnostic test for early-stage disease","volume":"393","author":"Sartini","year":"2012","journal-title":"Biol Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.radonc.2011.05.086","article-title":"Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances cellular radiation resistance","volume":"99","author":"Safwat","year":"2011","journal-title":"Radiother. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1093\/carcin\/bgq225","article-title":"Nicotinamide N-methyltransferase induces cellular invasion through activating matrix metalloproteinase-2 expression in clear cell renal cell carcinoma cells","volume":"32","author":"Tang","year":"2011","journal-title":"Carcinogenesis"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3177\/jnsv.56.83","article-title":"Interferon-gamma elevates nicotinamide N-methyltransferase activity and nicotinamide level in human glioma cells","volume":"56","author":"Yamada","year":"2010","journal-title":"J. Nutr. Sci. Vitam."},{"key":"ref_111","first-page":"15","article-title":"Nicotinamide N-Methyltransferase upregulation correlates with tumour differentiation in oral squamous cell carcinoma","volume":"25","author":"Emanuelli","year":"2010","journal-title":"Histol. Histopathol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s00432-009-0563-y","article-title":"Serum levels of nicotinamide N-methyltransferase in patients with lung cancer","volume":"135","author":"Tomida","year":"2009","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1756-9966-28-20","article-title":"Expression of nicotinamide N-methyltransferase in hepatocellular carcinoma is associated with poor prognosis","volume":"28","author":"Kim","year":"2009","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"6679","DOI":"10.1038\/onc.2008.264","article-title":"Overlapping gene expression profiles of cell migration and tumor invasion in human bladder cancer identify metallothionein 1E and nicotinamide N-methyltransferase as novel regulators of cell migration","volume":"27","author":"Wu","year":"2008","journal-title":"Oncogene"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00432-007-0318-6","article-title":"Stat3 up-regulates expression of nicotinamide N-methyltransferase in human cancer cells","volume":"134","author":"Tomida","year":"2008","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2119\/2007-00035.Sartini","article-title":"Nicotinamide N-methyltransferase upregulation inversely correlates with lymph node metastasis in oral squamous cell carcinoma","volume":"13","author":"Sartini","year":"2007","journal-title":"Mol. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1016\/j.juro.2006.07.046","article-title":"Identification of nicotinamide N-methyltransferase as a novel tumor marker for renal clear cell carcinoma","volume":"176","author":"Sartini","year":"2006","journal-title":"J. Urol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"6550","DOI":"10.1158\/1078-0432.CCR-05-0983","article-title":"Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer","volume":"11","author":"Roessler","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1210\/me.2004-0215","article-title":"Activation of nicotinamide N-methyltransferase gene promoter by hepatocyte nuclear factor-1beta in human papillary thyroid cancer cells","volume":"19","author":"Xu","year":"2005","journal-title":"Mol. Endocrinol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1002\/ijc.10631","article-title":"A potential role of heat shock proteins and nicotinamide N-methyl transferase in predicting response to radiation in bladder cancer","volume":"101","author":"Kassem","year":"2002","journal-title":"Int. J. Cancer."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1349-7006.1998.tb03267.x","article-title":"Increased hepatic nicotinamide N-methyltransferase activity as a marker of cancer cachexia in mice bearing colon 26 adenocarcinoma","volume":"89","author":"Okamura","year":"1998","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1159\/000217868","article-title":"Characterization of nicotinamide methyltransferase in livers of mice bearing Ehrlich ascites tumors: Preferential increase of activity","volume":"15","author":"Hanazawa","year":"1994","journal-title":"Tumour Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1111\/j.1349-7006.1991.tb01793.x","article-title":"N1-methylnicotinamide level in the blood after nicotinamide loading as further evidence for malignant tumor burden","volume":"82","author":"Nakagawa","year":"1991","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Balaziova, E., Vymola, P., Hrabal, P., Mateu, R., Zubal, M., Tomas, R., Netuka, D., Kramar, F., Zemanova, Z., and Svobodova, K. (2021). Fibroblast Activation Protein Expressing Mesenchymal Cells Promote Glioblastoma Angiogenesis. Cancers, 13.","DOI":"10.3390\/cancers13133304"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e523","DOI":"10.1097\/RLU.0000000000003810","article-title":"Feasibility and Therapeutic Potential of 177Lu-Fibroblast Activation Protein Inhibitor-46 for Patients With Relapsed or Refractory Cancers: A Preliminary Study","volume":"46","author":"Assadi","year":"2021","journal-title":"Clin. Nucl. Med."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Kesch, C., Yirga, L., Dendl, K., Handke, A., Darr, C., Krafft, U., Radtke, J.P., Tschirdewahn, S., Szarvas, T., and Fazli, L. (2021). High fibroblast-activation-protein expression in castration-resistant prostate cancer supports the use of FAPI-molecular theranostics. Eur. J. Nucl. Med. Mol. Imaging.","DOI":"10.1007\/s00259-021-05423-y"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s41824-021-00106-1","article-title":"68Ga-FAPI-04 PET\/MR is helpful in differential diagnosis of pancreatitis from pancreatic malignancy compared to 18F-FDG PET\/CT: A case report","volume":"5","author":"Shou","year":"2021","journal-title":"Eur. J. Hybrid. Imaging"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Baum, R.P., Schuchardt, C., Singh, A., Chantadisai, M., Robiller, F.C., Zhang, J., Mueller, D., Eismant, A., Almaguel, F., and Zboralski, D. (2021). Feasibility, Biodistribution and Preliminary Dosimetry in Peptide-Targeted Radionuclide Therapy (PTRT) of Diverse Adenocarcinomas using (177)Lu-FAP-2286: First-in-Human Results. J. Nucl. Med., 62.","DOI":"10.2967\/jnumed.120.259192"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Wang, S., Zhou, X., Xu, X., Ding, J., Liu, S., Hou, X., Li, N., Zhu, H., and Yang, Z. (2021). Clinical translational evaluation of Al(18)F-NOTA-FAPI for fibroblast activation protein-targeted tumour imaging. Eur. J. Nucl. Med. Mol. Imaging.","DOI":"10.21203\/rs.3.rs-231262\/v1"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.1007\/s00259-021-05378-0","article-title":"68Ga-FAPI-PET\/CT in patients with various gynecological malignancies","volume":"48","author":"Dendl","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Jin, X., Wei, M., Wang, S., Wang, G., Lai, Y., Shi, Y., Zhang, Y., Yang, Z., and Wang, X. (2021). Detecting fibroblast activation proteins in lymphoma using (68)Ga-FAPI PET\/CT. J. Nucl. Med., 62.","DOI":"10.2967\/jnumed.121.262134"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41419-021-03823-4","article-title":"Colorectal cancer cell intrinsic fibroblast activation protein alpha binds to Enolase1 and activates NF-kappaB pathway to promote metastasis","volume":"12","author":"Yuan","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.radonc.2021.04.016","article-title":"68Ga-FAPI-PET\/CT improves diagnostic staging and radiotherapy planning of adenoid cystic carcinomas - Imaging analysis and histological validation","volume":"160","author":"Syed","year":"2021","journal-title":"Radiother. Oncol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Kessler, L., Ferdinandus, J., Hirmas, N., Bauer, S., Dirksen, U., Zarrad, F., Nader, M., Chodyla, M.K., Milosevic, A., and Umutlu, L. (2021). Ga-68-FAPI as diagnostic tool in sarcoma: Data from the FAPI-PET prospective observational trial. J. Nucl. Med., 62.","DOI":"10.2967\/jnumed.121.262096"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.1158\/1078-0432.CCR-20-4001","article-title":"Fibroblast Activation Protein alpha-Targeted CD40 Agonism Abrogates Systemic Toxicity and Enables Administration of High Doses to Induce Effective Antitumor Immunity","volume":"27","author":"Sum","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"3511","DOI":"10.1111\/jcmm.16434","article-title":"Nanoparticle formulation of mycophenolate mofetil achieves enhanced efficacy against hepatocellular carcinoma by targeting tumour-associated fibroblast","volume":"25","author":"Yang","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1021\/acs.jmedchem.0c02171","article-title":"Imaging of Fibroblast Activation Protein in Cancer Xenografts Using Novel (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine-Based Small Molecules","volume":"64","author":"Slania","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Sitia, L., Bonizzi, A., Mazzucchelli, S., Negri, S., Sottani, C., Grignani, E., Rizzuto, M.A., Prosperi, D., Sorrentino, L., and Morasso, C. (2021). Selective Targeting of Cancer-Associated Fibroblasts by Engineered H-Ferritin Nanocages Loaded with Navitoclax. Cells, 10.","DOI":"10.3390\/cells10020328"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1038\/s41598-021-81465-4","article-title":"Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer","volume":"11","author":"Katsube","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"779","DOI":"10.2967\/jnumed.120.253062","article-title":"Impact of 68Ga-FAPI PET\/CT Imaging on the Therapeutic Management of Primary and Recurrent Pancreatic Ductal Adenocarcinomas","volume":"62","author":"Naumann","year":"2021","journal-title":"J. Nucl. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/s00259-020-04882-z","article-title":"Fibroblast imaging of hepatic carcinoma with (68)Ga-FAPI-04 PET\/CT: A pilot study in patients with suspected hepatic nodules","volume":"48","author":"Shi","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Tansi, F.L., R\u00fcger, R., B\u00f6hm, C., Steiniger, F., Raasch, M., Mosig, A.S., Kontermann, R.E., Teichgr\u00e4ber, U.K., Fahr, A., and Hilger, I. (2020). Rapid Target Binding and Cargo Release of Activatable Liposomes Bearing HER2 and FAP Single-Chain Antibody Fragments Reveal Potentials for Image-Guided Delivery to Tumors. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12100972"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1007\/s11307-020-01548-y","article-title":"Impact of Primary Staging with Fibroblast Activation Protein Specific Enzyme Inhibitor (FAPI)-PET\/CT on Radio-Oncologic Treatment Planning of Patients with Esophageal Cancer","volume":"22","author":"Ristau","year":"2020","journal-title":"Mol. Imaging Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s41181-020-00102-z","article-title":"Targeting fibroblast activation protein (FAP): Next generation PET radiotracers using squaramide coupled bifunctional DOTA and DATA(5m) chelators","volume":"5","author":"Moon","year":"2020","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e000238","DOI":"10.1136\/jitc-2019-000238","article-title":"Fibroblast activation protein-targeted-4-1BB ligand agonist amplifies effector functions of intratumoral T cells in human cancer","volume":"8","author":"Uhlenbrock","year":"2020","journal-title":"J. Immunother. Cancer."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1007\/s00259-020-04859-y","article-title":"Fibroblast activation protein inhibitor (FAPI) PET for diagnostics and advanced targeted radiotherapy in head and neck cancers","volume":"47","author":"Syed","year":"2020","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.2967\/jnumed.120.242958","article-title":"Targeting Fibroblast Activation Protein: Radiosynthesis and Preclinical Evaluation of an (18)F-Labeled FAP Inhibitor","volume":"61","author":"Toms","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.2967\/jnumed.119.239731","article-title":"Design and Development of 99mTc-Labeled FAPI Tracers for SPECT Imaging and 188Re Therapy","volume":"61","author":"Lindner","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.2967\/jnumed.119.236786","article-title":"Radiation Dosimetry and Biodistribution of (68)Ga-FAPI-46 PET Imaging in Cancer Patients","volume":"61","author":"Meyer","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"801","DOI":"10.2967\/jnumed.119.227967","article-title":"(68)Ga-FAPI PET\/CT: Tracer Uptake in 28 Different Kinds of Cancer","volume":"60","author":"Kratochwil","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"386","DOI":"10.2967\/jnumed.118.215913","article-title":"(68)Ga-FAPI PET\/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with Various Cancers","volume":"60","author":"Giesel","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1158\/1535-7163.MCT-15-0647","article-title":"RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis","volume":"15","author":"Wartha","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1021\/ml300410d","article-title":"Selective Inhibitors of Fibroblast Activation Protein (FAP) with a (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine Scaffold","volume":"4","author":"Jansen","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.4161\/cbt.6.11.4874","article-title":"Phase II trial of single agent Val-boroPro (Talabostat) inhibiting Fibroblast Activation Protein in patients with metastatic colorectal cancer","volume":"6","author":"Narra","year":"2007","journal-title":"Cancer Biol. Ther."},{"key":"ref_155","first-page":"1639","article-title":"A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer","volume":"9","author":"Scott","year":"2003","journal-title":"Clin. Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/20\/5088\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:11:53Z","timestamp":1760166713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/20\/5088"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,12]]},"references-count":155,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["cancers13205088"],"URL":"https:\/\/doi.org\/10.3390\/cancers13205088","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2021,10,12]]}}}