{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T06:13:02Z","timestamp":1793859182632,"version":"4.6.1"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802641"],"award-info":[{"award-number":["81802641"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"DOI":"10.1007\/s12672-025-03779-3","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T11:41:01Z","timestamp":1763984461000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A pancancer analysis reveals the oncogenic role of glutaminase 1 (GLS1) in tumor metabolism and immune evasion: a bioinformatics analysis"],"prefix":"10.1007","volume":"16","author":[{"given":"Jianjun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikai","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangsheng","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"3779_CR1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cmet.2007.10.002","volume":"7","author":"RJ DeBerardinis","year":"2008","unstructured":"DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008;7:11\u201320.","journal-title":"Cell Metab"},{"key":"3779_CR2","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.cell.2017.04.004","volume":"169","author":"MD Buck","year":"2017","unstructured":"Buck MD, Sowell RT, Kaech SM, Pearce EL. Metabolic instruction of immunity. Cell. 2017;169:570\u201386.","journal-title":"Cell"},{"key":"3779_CR3","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.cmet.2017.06.004","volume":"26","author":"G Andrejeva","year":"2017","unstructured":"Andrejeva G, Rathmell JC. Similarities and distinctions of cancer and immune metabolism in inflammation and tumors. Cell Metab. 2017;26:49\u201370.","journal-title":"Cell Metab"},{"key":"3779_CR4","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1126\/science.aar5986","volume":"360","author":"A Muir","year":"2018","unstructured":"Muir A, Vander Heiden MG. The nutrient environment affects therapy. Science. 2018;360:962\u20133.","journal-title":"Science"},{"key":"3779_CR5","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.molmed.2017.11.005","volume":"24","author":"L Zhang","year":"2018","unstructured":"Zhang L, Romero P. Metabolic control of CD8(+) T cell fate decisions and antitumor immunity. Trends Mol Med. 2018;24:30\u201348.","journal-title":"Trends Mol Med"},{"key":"3779_CR6","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.immuni.2016.07.009","volume":"45","author":"NE Scharping","year":"2016","unstructured":"Scharping NE, Menk AV, Moreci RS, Whetstone RD, Dadey RE, Watkins SC, Ferris RL, Delgoffe GM. The tumor microenvironment represses T cell mitochondrial biogenesis to drive intratumoral T cell metabolic insufficiency and dysfunction. Immunity. 2016;45:374\u201388.","journal-title":"Immunity"},{"key":"3779_CR7","doi-asserted-by":"publisher","first-page":"400","DOI":"10.4049\/jimmunol.1701041","volume":"200","author":"A Sugiura","year":"2018","unstructured":"Sugiura A, Rathmell JC. Metabolic barriers to T cell function in tumors. J Immunol. 2018;200:400\u20137.","journal-title":"J Immunol"},{"key":"3779_CR8","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/j.cell.2013.05.016","volume":"153","author":"CH Chang","year":"2013","unstructured":"Chang CH, et al. Posttranscriptional control of T cell effector function by aerobic Glycolysis. Cell. 2013;153:1239\u201351.","journal-title":"Cell"},{"key":"3779_CR9","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1016\/j.celrep.2018.01.040","volume":"22","author":"AV Menk","year":"2018","unstructured":"Menk AV, et al. Early TCR signaling induces rapid aerobic Glycolysis enabling distinct acute T cell effector functions. Cell Rep. 2018;22:1509\u201321.","journal-title":"Cell Rep"},{"key":"3779_CR10","doi-asserted-by":"publisher","first-page":"3678","DOI":"10.1172\/JCI69600","volume":"123","author":"CT Hensley","year":"2013","unstructured":"Hensley CT, Wasti AT, DeBerardinis RJ. Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest. 2013;123:3678\u201384.","journal-title":"J Clin Invest"},{"key":"3779_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF00230880","volume":"113","author":"MA Medina","year":"1992","unstructured":"Medina MA, S\u00e1nchez-Jim\u00e9nez F, M\u00e1rquez J, Rodr\u00edguez Quesada A, de N\u00fa\u00f1ez I. Relevance of glutamine metabolism to tumor cell growth. Mol Cell Biochem. 1992;113:1\u201315.","journal-title":"Mol Cell Biochem"},{"key":"3779_CR12","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.jss.2005.07.013","volume":"131","author":"BC Fuchs","year":"2006","unstructured":"Fuchs BC, Bode BP. Stressing out over survival: glutamine as an apoptotic modulator. J Surg Res. 2006;131:26\u201340.","journal-title":"J Surg Res"},{"key":"3779_CR13","unstructured":"Ashby JM. Cancer cell metabolism connects epigenetic modifications to transcriptional regulation. FEBS J; 2021."},{"key":"3779_CR14","doi-asserted-by":"crossref","unstructured":"Xu L, et al. A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer. Proc Natl Acad Sci USA; 2021;118.","DOI":"10.1073\/pnas.2012748118"},{"key":"3779_CR15","doi-asserted-by":"publisher","unstructured":"Saha SA-O, Islam SA-O, Abdullah-Al-Wadud M, Islam S, Ali F, Park. K.A.-O. Multiomics analysis reveals that GLS and GLS2 differentially modulate the clinical outcomes of cancer. 355. https:\/\/doi.org\/10.3390\/jcm8030355.","DOI":"10.3390\/jcm8030355"},{"key":"3779_CR16","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1038\/onc.2016.364","volume":"36","author":"A Cacace","year":"2017","unstructured":"Cacace A, Sboarina M, Vazeille T, Sonveaux P. Glutamine activates STAT3 to control cancer cell proliferation independently of glutamine metabolism. Oncogene. 2017;36:2074\u201384.","journal-title":"Oncogene"},{"key":"3779_CR17","unstructured":"Byun JK, et al. Inhibition of glutamine utilization synergizes with immune checkpoint inhibitor to promote antitumor immunity."},{"key":"3779_CR18","doi-asserted-by":"publisher","unstructured":"Zou JA-O, et al. Glutamine metabolism regulators associated with cancer development and the tumor microenvironment: a pan-cancer multi-omics analysis. 1305. https:\/\/doi.org\/10.3390\/genes12091305.","DOI":"10.3390\/genes12091305"},{"key":"3779_CR19","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.cmet.2018.06.003","volume":"28","author":"A Daemen","year":"2018","unstructured":"Daemen A, et al. Pan-Cancer metabolic signature predicts Co-Dependency on glutaminase and de Novo glutathione synthesis linked to a High-Mesenchymal cell state. Cell Metab. 2018;28:383\u2013e3999.","journal-title":"Cell Metab"},{"key":"3779_CR20","doi-asserted-by":"publisher","first-page":"424","DOI":"10.3389\/fonc.2020.00424","volume":"10","author":"KW Bi","year":"2020","unstructured":"Bi KW, Wei XG, Qin XX, Li B. BTK has potential to be a prognostic factor for lung adenocarcinoma and an indicator for tumor microenvironment remodeling: A study based on TCGA data mining. Front Oncol. 2020;10:424.","journal-title":"Front Oncol"},{"key":"3779_CR21","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1186\/s12935-021-02350-8","volume":"21","author":"P Yang","year":"2021","unstructured":"Yang P, Chen W, Xu H, Yang J, Jiang J, Jiang Y, Xu G. Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway. Cancer Cell Int. 2021;21:635.","journal-title":"Cancer Cell Int"},{"key":"3779_CR22","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.ccell.2023.01.009","volume":"41","author":"EN Arner","year":"2023","unstructured":"Arner EN, Rathmell JC. Metabolic programming and immune suppression in the tumor microenvironment. Cancer Cell. 2023;41:421\u201333.","journal-title":"Cancer Cell"},{"key":"3779_CR23","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","volume":"24","author":"M Binnewies","year":"2018","unstructured":"Binnewies M, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24:541\u201350.","journal-title":"Nat Med"},{"key":"3779_CR24","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/nature12626","volume":"501","author":"MR Junttila","year":"2013","unstructured":"Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501:346\u201354.","journal-title":"Nature"},{"key":"3779_CR25","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1038\/nrc2540","volume":"8","author":"JA Bertout","year":"2008","unstructured":"Bertout JA, Patel SA, Simon MC. The impact of O2 availability on human cancer. Nat Rev Cancer. 2008;8:967\u201375.","journal-title":"Nat Rev Cancer"},{"key":"3779_CR26","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nrc3038","volume":"11","author":"WH Koppenol","year":"2011","unstructured":"Koppenol WH, Bounds PL, Dang CV. Otto warburg\u2019s contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011;11:325\u201337.","journal-title":"Nat Rev Cancer"},{"key":"3779_CR27","doi-asserted-by":"crossref","unstructured":"DePeaux K, Delgoffe GM. Metabolic barriers to cancer immunotherapy. Nat Rev Immunol; 2021.","DOI":"10.1038\/s41577-021-00541-y"},{"key":"3779_CR28","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/onc.2009.358","volume":"29","author":"RJ DeBerardinis","year":"2010","unstructured":"DeBerardinis RJ, Cheng T. Q\u2019s next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene. 2010;29:313\u201324.","journal-title":"Oncogene"},{"key":"3779_CR29","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1083\/jcb.200703099","volume":"178","author":"M Yuneva","year":"2007","unstructured":"Yuneva M, Zamboni N, Oefner P, Sachidanandam R, Lazebnik Y. Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. J Cell Biol. 2007;178:93\u2013105.","journal-title":"J Cell Biol"},{"key":"3779_CR30","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1038\/nature07823","volume":"458","author":"P Gao","year":"2009","unstructured":"Gao P, et al. c-Myc suppression of miR-23a\/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature. 2009;458:762\u20135.","journal-title":"Nature"},{"key":"3779_CR31","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.molcel.2012.05.043","volume":"47","author":"RV Dur\u00e1n","year":"2012","unstructured":"Dur\u00e1n RV, Oppliger W, Robitaille AM, Heiserich L, Skendaj R, Gottlieb E, Hall MN. Glutaminolysis activates Rag-mTORC1 signaling. Mol Cell. 2012;47:349\u201358.","journal-title":"Mol Cell"},{"key":"3779_CR32","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.molcel.2016.05.029","volume":"62","author":"JP Etchegaray","year":"2016","unstructured":"Etchegaray JP, Mostoslavsky R. Interplay between metabolism and epigenetics: A nuclear adaptation to environmental changes. Mol Cell. 2016;62:695\u2013711.","journal-title":"Mol Cell"},{"key":"3779_CR33","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.cell.2013.03.004","volume":"153","author":"WG Kaelin Jr","year":"2013","unstructured":"Kaelin WG Jr., McKnight SL. Influence of metabolism on epigenetics and disease. Cell. 2013;153:56\u201369.","journal-title":"Cell"},{"key":"3779_CR34","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.cell.2013.12.019","volume":"156","author":"H Wu","year":"2014","unstructured":"Wu H, Zhang Y. Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell. 2014;156:45\u201368.","journal-title":"Cell"},{"key":"3779_CR35","doi-asserted-by":"publisher","first-page":"e2002810","DOI":"10.1371\/journal.pbio.2002810","volume":"15","author":"TQ Tran","year":"2017","unstructured":"Tran TQ, Ishak Gabra MB, Lowman XH, Yang Y, Reid MA, Pan M, O\u2019Connor TR, Kong M. Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through Inhibition of ALKBH enzymes. PLoS Biol. 2017;15:e2002810.","journal-title":"PLoS Biol"},{"key":"3779_CR36","unstructured":"Hwang S, Yang S, Kim MA-O, Hong Y, Kim B, Lee EK, Jeong SA-O. Mitochondrial glutamine metabolism regulates sensitivity of cancer cells after chemotherapy via Amphiregulin."},{"key":"3779_CR37","first-page":"1350","volume-title":"Cancer immunotherapy using checkpoint Blockade","author":"A Ribas","year":"2018","unstructured":"Ribas A, Wolchok J. Cancer immunotherapy using checkpoint Blockade. Volume 359. New York, N.Y.: Science; 2018. pp. 1350\u20135."},{"key":"3779_CR38","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.immuni.2018.03.023","volume":"48","author":"V Thorsson","year":"2018","unstructured":"Thorsson V, et al. The immune landscape of cancer. Immunity. 2018;48:812\u2013e83014.","journal-title":"Immunity"},{"key":"3779_CR39","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/s41568-021-00378-6","volume":"21","author":"I Mart\u00ednez-Reyes","year":"2021","unstructured":"Mart\u00ednez-Reyes I, Chandel NS. Cancer metabolism: looking forward. Nat Rev Cancer. 2021;21:669\u201380.","journal-title":"Nat Rev Cancer"},{"key":"3779_CR40","doi-asserted-by":"publisher","first-page":"4815","DOI":"10.1158\/0008-5472.CAN-20-0600","volume":"80","author":"Y Zhao","year":"2020","unstructured":"Zhao Y, et al. 5-Fluorouracil enhances the antitumor activity of the glutaminase inhibitor CB-839 against PIK3CA-Mutant colorectal cancers. Cancer Res. 2020;80:4815\u201327.","journal-title":"Cancer Res"},{"key":"3779_CR41","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1158\/1535-7163.MCT-13-0870","volume":"13","author":"MI Gross","year":"2014","unstructured":"Gross MI, et al. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther. 2014;13:890\u2013901.","journal-title":"Mol Cancer Ther"},{"key":"3779_CR42","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1080\/09553002.2018.1558299","volume":"95","author":"G Boysen","year":"2019","unstructured":"Boysen G, Jamshidi-Parsian A, Davis MA, Siegel ER, Simecka CM, Kore RA, Dings RPM, Griffin RJ. Glutaminase inhibitor CB-839 increases radiation sensitivity of lung tumor cells and human lung tumor xenografts in mice. Int J Radiat Biol. 2019;95:436\u201342.","journal-title":"Int J Radiat Biol"},{"key":"3779_CR43","doi-asserted-by":"publisher","first-page":"35863","DOI":"10.18632\/oncotarget.16262","volume":"8","author":"RM Thompson","year":"2017","unstructured":"Thompson RM, et al. Glutaminase inhibitor CB-839 synergizes with Carfilzomib in resistant multiple myeloma cells. Oncotarget. 2017;8:35863\u201376.","journal-title":"Oncotarget"},{"key":"3779_CR44","doi-asserted-by":"crossref","unstructured":"Jin H, et al. A powerful drug combination strategy targeting glutamine addiction for the treatment of human liver cancer. Elif. 2020;9.","DOI":"10.7554\/eLife.56749"},{"key":"3779_CR45","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/s41467-020-14374-1","volume":"11","author":"P Lee","year":"2020","unstructured":"Lee P, et al. Targeting glutamine metabolism slows soft tissue sarcoma growth. Nat Commun. 2020;11:498.","journal-title":"Nat Commun"},{"key":"3779_CR46","doi-asserted-by":"crossref","unstructured":"Lodi A, et al. Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism. NPJ Precis Oncol. 2017;1:18.","DOI":"10.1038\/s41698-017-0024-z"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-025-03779-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-025-03779-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-025-03779-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T11:41:05Z","timestamp":1763984465000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-025-03779-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,24]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3779"],"URL":"https:\/\/doi.org\/10.1007\/s12672-025-03779-3","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,24]]},"assertion":[{"value":"23 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study uses de-identified, publicly available data from TCGA and GEO datasets. The data was originally collected with participant consent for secondary research. Our protocol complies with the database\u2019s Data Use Agreement and focuses on aggregate analysis. No participant re-contact or re-identification will occur. This study does not involve direct participation of human subjects or individuals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2156"}}