GTP Cyclohydrolase Drives Breast Cancer Development and Promotes EMT in an Enzyme-Independent Manner

https://m2.mtmt.hu/ hun 2026-09-22 05:43 JournalArticle 34425894 VALIDATED true 0 false 2026-08-31T09:00:09.981+0000 2023-12-08T10:20:42.949+0000 2023-12-08T10:17:05.131+0000 true 10062250 Molnár-Taga Márta /api/admin/10062250 Admin Molnár-Taga Márta (SE 4-es admin) true 10062250 2024-09-09T08:00:16.821+0000 2023-12-08T10:20:42.959+0000 true 10062250 Molnár-Taga Márta /api/admin/10062250 Admin Molnár-Taga Márta (SE 4-es admin) true 10062250 Admin 10014568 /api/admin/10014568 Vándor Andrea (VA, admin) Vándor Andrea true 10014568 true 2024-04-04T10:42:37.228+0000 true false true 24 24 /api/publicationtype/24 PublicationType Folyóiratcikk 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType Folyóiratcikk 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType Szakcikk (Folyóiratcikk) 101 true 10000059 true 1 /api/category/1 Category Tudományos true 1 Wang, Zijing GTP Cyclohydrolase Drives Breast Cancer Development and Promotes EMT in an Enzyme-Independent Manner true true /api/journal/912 REVIEWED CANCER RESEARCH 0008-5472 1538-7445 true false 912 false 912 true 0008-5472 1538-7445 Journal FOREIGN 83 20 3400 3413 3400 14 2023 GTP cyclohydrolase functions as an oncogene in breast cancer and binds vimentin to induce epithelial-to-mesenchymal transition independently of its enzyme activity, which confers targetable vulnerabilities for developing breast cancer treatment strategies. GTP cyclohydrolase (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis. The catalysis of BH4 biosynthesis is tightly regulated for physiological neurotransmission, inflammation, and vascular tone. Paradoxically, BH4 has emerged as an oncometabolite regulating tumor growth, but the effects on tumor development remain controversial. Here, we found that GCH1 potentiated the growth of triple-negative breast cancer (TNBC) and HER2+ breast cancer and transformed nontumor breast epithelial cells. Independent of BH4 production, GCH1 protein induced epithelial-to-mesenchymal transition by binding to vimentin (Vim), which was mediated by HSP90. Conversely, GCH1 ablation impaired tumor growth, suppressed Vim in TNBC, and inhibited EGFR/ERK signaling while activating the p53 pathway in estrogen receptor-positive tumor cells. GCH1 deficiency increases tumor cell sensitivity to HSP90 inhibition and endocrine treatments. In addition, high GCH1 correlated with poor breast cancer survival. Together, this study reveals an enzyme-independent oncogenic role of GCH1, presenting it as a potential target for therapeutic development.Significance: GTP cyclohydrolase functions as an oncogene in breast cancer and binds vimentin to induce epithelial-to-mesenchymal transition independently of its enzyme activity, which confers targetable vulnerabilities for developing breast cancer treatment strategies. true true 2023 true true true false true false PAY 2026-08-31 false 17 0 17 16 1 17 17 16 16 17 17 16 16 16 1 0 17 16 17 16 0 2 2 Folyóiratcikk Journal Article 24 17 Könyvrészlet Chapter in Book 25 0 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2023 0 1 1 1 1 2024 0 3 3 3 3 2025 0 6 6 6 6 2026 0 7 6 7 6 D1 false false false false 2023-12-07T10:20:42.798+0000 Bioinformatika Tanszék (SE / AOK / I); Enzimológiai Intézet (TTK); Gyermekgyógyászati Klinika (SE / AOK / K) 1 26 3 17 0 true 10014568 Language 10002 /api/language/10002 Angol Angol English true 2 true PersonAuthorship 113182915 /api/authorship/113182915 Wang, Zijing 1 0.05882353 true false false Wang Zijing true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182916 /api/authorship/113182916 Zhang, Nan 2 0.05882353 false false false Zhang Nan true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182917 /api/authorship/113182917 Zhang, Miao 3 0.05882353 false false false Zhang Miao true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182918 /api/authorship/113182918 Jiang, Yao 4 0.05882353 false false false Jiang Yao true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182919 /api/authorship/113182919 Ng, Aik Seng 5 0.05882353 false false false Ng Aik Seng true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182920 /api/authorship/113182920 Bridges, Esther 6 0.05882353 false false false Bridges Esther true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182921 /api/authorship/113182921 Zhang, Wei 7 0.05882353 false false false Zhang Wei true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182922 /api/authorship/113182922 Zeng, Xin 8 0.05882353 false false false Zeng Xin true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182923 /api/authorship/113182923 Luo, Qi 9 0.05882353 false false false Luo Qi true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182924 /api/authorship/113182924 Liang, Jiabien 10 0.05882353 false false false Liang Jiabien true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182925 /api/authorship/113182925 Gyorffy, Balazs [Győrffy, Balázs (Onkológia), szerző] Enzimológiai Intézet (TTK); Bioinformatika Tanszék (SE / AOK / I); Gyermekgyógyászati Klinika (SE / AOK / K) 11 0.059 false false false Author 10000109 /api/author/10000109 Győrffy Balázs (Onkológia) Győrffy Balázs true 10000109 true Gyorffy Balazs true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182926 /api/authorship/113182926 Hublitz, Philip 12 0.05882353 false false false Hublitz Philip true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182927 /api/authorship/113182927 Liang, Zhu 13 0.05882353 false false false Liang Zhu true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182928 /api/authorship/113182928 Fischer, Roman 14 0.05882353 false false false Fischer Roman true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182929 /api/authorship/113182929 Kerr, David 15 0.05882353 false false false Kerr David true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182930 /api/authorship/113182930 Harris, Adrian L. 16 0.05882353 false false false Harris Adrian L. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 113182931 /api/authorship/113182931 Cai, Shijie ✉ 17 0.05882353 false true true Cai Shijie true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PublicationIdentifier 25088690 /api/publicationidentifier/25088690 DOI: 10.1158/0008-5472.CAN-22-3471 PlainSource 6 /api/publicationsource/6 DOI PublicationSourceType 10001 /api/publicationsourcetype/10001 DOI true true true DOI DOI https://doi.org/@@@ true true 6 true PAY IDENTICAL 10.1158/0008-5472.CAN-22-3471 https://doi.org/10.1158/0008-5472.CAN-22-3471 false true PublicationIdentifier 25088691 /api/publicationidentifier/25088691 WoS: 001101112600008 PlainSource 1 /api/publicationsource/1 WoS PublicationSourceType 10003 /api/publicationsourcetype/10003 Indexelő adatbázis false true true WoS WoS https://www.webofscience.com/wos/woscc/full-record/@@@ true true 1 true IDENTICAL 001101112600008 https://www.webofscience.com/wos/woscc/full-record/001101112600008 false true PublicationIdentifier 27067742 /api/publicationidentifier/27067742 Scopus: 85179979057 PlainSource 3 /api/publicationsource/3 Scopus PublicationSourceType 10003 /api/publicationsourcetype/10003 Indexelő adatbázis false true true Scopus Scopus http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-@@@ true true 3 true IDENTICAL 85179979057 http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85179979057 false true PublicationIdentifier 25088692 /api/publicationidentifier/25088692 PubMed: 37463466 PlainSource 17 /api/publicationsource/17 PubMed PublicationSourceType 10003 /api/publicationsourcetype/10003 Indexelő adatbázis false true true PubMed PubMed http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=@@@&dopt=Abstract true true 17 true IDENTICAL 37463466 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=37463466&dopt=Abstract false true Keyword 181 /api/keyword/181 EXPRESSION true 181 true Keyword 228 /api/keyword/228 TETRAHYDROBIOPTERIN true 228 true Keyword 233 /api/keyword/233 PEROXYNITRITE true 233 true Keyword 312 /api/keyword/312 ENDOTHELIAL-CELLS true 312 true Keyword 510 /api/keyword/510 resistance true 510 true Keyword 621 /api/keyword/621 ACTIVATION true 621 true Keyword 1002240 /api/keyword/1002240 HSP90 true 1002240 true Keyword 1071862 /api/keyword/1071862 PHASE-II TRIAL true 1071862 true Keyword 1526781 /api/keyword/1526781 tanespimycin true true SjrRating 11360643 /api/sjrrating/11360643 sjr:D1 (2023) Scopus - Cancer Research CANCER RESEARCH 0008-5472 1538-7445 21 0.1 journal RatingType 10002 /api/ratingtype/10002 sjr sjr true true ClassificationExternal 1306 /api/classificationexternal/1306 Scopus - Cancer Research true 1306 true D1 DIRECT true true Reference 47824689 /api/reference/47824689 1. 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(2023) CANCER RESEARCH 0008-5472 1538-7445 83 20 3400-3413<div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" >Wang Zijing </span> ;    <span class="author-name" >Zhang Nan </span> ;    <span class="author-name" >Zhang Miao </span> ;    <span class="author-name" >Jiang Yao </span> ;    <span class="author-name" >Ng Aik Seng </span> ;    <span class="author-name" >Bridges Esther </span> ;    <span class="author-name" >Zhang Wei </span> ;    <span class="author-name" >Zeng Xin </span> ;    <span class="author-name" >Luo Qi </span> ;    <span class="author-name" >Liang Jiabien </span> ;    <span class="author-name" mtid="10000109"><a href="/gui2/?type=authors&mode=browse&sel=10000109" target="_blank">Gyorffy Balazs (<span class="authorship-author-name">Győrffy Balázs</span> <span class="authorAux-mtmt"> Onkológia</span>) </a> </span> <span class="author-affil"><span title="Természettudományi Kutatóközpont">TTK</span>/Enzimológiai Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Bioinformatika Tanszék; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/Gyermekgyógyászati Klinika</span> ;    <span class="author-name" >Hublitz Philip </span> ;    <span class="author-name" >Liang Zhu </span> ;    <span class="author-name" >Fischer Roman </span> ;    <span class="author-name" >Kerr David </span> ;    <span class="author-name" >Harris Adrian L. </span> ;    <span class="author-name" >Cai Shijie ✉ </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;34425894" target="_blank">GTP Cyclohydrolase Drives Breast Cancer Development and Promotes EMT in an Enzyme-Independent Manner</a></div> <div> <span class="journal-title">CANCER RESEARCH</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0008-5472">0008-5472</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1538-7445">1538-7445</a>)</span>: <span class="journal-volume">83</span> <span class="journal-issue">20</span> <span class="page"> pp 3400-3413 </span> <span class="year">(2023)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_PAY" title=" Fizetős "> <a style="color:blue" title="10.1158/0008-5472.CAN-22-3471" target="_blank" href="https://doi.org/10.1158/0008-5472.CAN-22-3471"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="001101112600008" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/001101112600008"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85179979057" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85179979057"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="37463466" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=37463466&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Cancer Research   SJR indikátor: D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Oncology   SJR indikátor: D1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 17</span> | Független: 16 | Függő: 1 | Nem jelölt: 0 | WoS jelölt: 16 | Scopus jelölt: 16 | WoS/Scopus jelölt: 17 | DOI jelölt: 17 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;34425894&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 2 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 34425894</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">WOS TAGGED</span> </div> <div class="lastModified">Utolsó módosítás: 2023.12.08. 11:20 Molnár-Taga Márta (SE 4-es admin) </div> <div class="lockedBy">Központi kezelésű 2024.04.04. 12:42 Vándor Andrea (VA, admin) </div> </div></div>