{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:19:52Z","timestamp":1770747592177,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cancer cells show a dynamic metabolic landscape, requiring a sufficient supply of nucleotides to proliferate. They are highly dependent on de novo purine biosynthetic pathways for their nucleotide requirements. Phosphoribosyl pyrophosphate amidotransferase (PPAT), catalyzing the first step of de novo purine biosynthesis, is highly expressed in various cancers. We observed an increased expression of PPAT in nasopharyngeal carcinoma (NPC). Moreover, our ribonucleic acid sequencing analysis showed high PPAT expression in Epstein\u2013Barr virus\u2010positive NPC, which was supported by in\u00a0vitro analysis. Through a gene knockdown study, we showed that the suppression of <jats:italic>PPAT<\/jats:italic> expression reduced the proliferation and invasion of NPC cells. We also demonstrated the regulation of PPAT by glutamine, a cosubstrate for PPAT. A glutamine antagonist, 6\u2010diazo\u20105\u2010oxo\u2010L\u2010norleucine, blocked glutamine\u2010mediated induction of PPAT and reduced NPC cell proliferation. Immunohistochemical analysis of PPAT in NPC tissues revealed increased expression of PPAT with disease progression, which was significantly associated with poor prognosis. In summary, this study highlighted the biological function of PPAT in NPC, establishing its potential as a novel prognostic biomarker for aggressive NPC and a promising therapeutic target.<\/jats:p>","DOI":"10.1111\/cas.16314","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T15:59:12Z","timestamp":1724860752000},"page":"3587-3595","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phosphoribosyl pyrophosphate amidotransferase: Novel biomarker and therapeutic target for nasopharyngeal carcinoma"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5197-1025","authenticated-orcid":false,"given":"Yuki","family":"Kitagawa","sequence":"first","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9066-0787","authenticated-orcid":false,"given":"Satoru","family":"Kondo","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Fukuyo","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Graduate School of Medicine Chiba University  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kousho","family":"Wakae","sequence":"additional","affiliation":[{"name":"Department of Virology II National Institute of Infectious Diseases  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5711-7240","authenticated-orcid":false,"given":"Hirotomo","family":"Dochi","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harue","family":"Mizokami","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigetaka","family":"Komura","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiji","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Hirai","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayoshi","family":"Ueno","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhira","family":"Endo","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naohiro","family":"Wakisaka","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6980-5515","authenticated-orcid":false,"given":"Atsushi","family":"Kaneda","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Graduate School of Medicine Chiba University  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomokazu","family":"Yoshizaki","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science Kanazawa University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CANLET.2013.05.018"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.60.7846"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4448"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1679"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BBADIS.2022.166598"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.38"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.123.3191.309"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.8.6.519"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15136-9"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(69)90067-1"},{"issue":"5","key":"e_1_2_10_12_1","first-page":"587","article-title":"Critical roles of glutamine as nitrogen donors in purine and pyrimidine nucleotide synthesis: asparaginase treatment in childhood acute lymphoblastic leukemia","volume":"20","author":"Cory JG","year":"2006","journal-title":"In Vivo"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2012.76.010900"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-092910-154237"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11050688"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.4149\/neo_2016_504"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S253137"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4352"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/CAS.15440"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-17-0134"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0953-6"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-08211-x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"crossref","unstructured":"LuckySS LawM LuiMH et\u00a0al.Patient\u2010derived nasopharyngeal cancer organoids for disease modeling and radiation Dose optimization.2021;11:622244. doi:10.3389\/fonc.2021.622244","DOI":"10.3389\/fonc.2021.622244"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CANLET.2012.12.002"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113702"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/SCIENCE.1259472"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5900"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2334"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.08.020"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25431"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.5.4371-4378.1998"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003361"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.2353\/AJPATH.2007.060798"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/BMT.2012.244"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S340758"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.TIBS.2010.05.003"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004715"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.15252\/EMBJ.201696151"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69600"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.16314","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T03:09:09Z","timestamp":1730689749000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.16314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,28]]},"references-count":39,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/cas.16314"],"URL":"https:\/\/doi.org\/10.1111\/cas.16314","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,28]]},"assertion":[{"value":"2024-02-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}