{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T20:47:02Z","timestamp":1785703622690,"version":"3.56.0"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ligne national contre le cancer","award":["equipe labelisee"],"award-info":[{"award-number":["equipe labelisee"]}]},{"name":"UNIVERSIDAD DE BUENOS AIRES-UBACYT 2020","award":["No. 20720190100005BA"],"award-info":[{"award-number":["No. 20720190100005BA"]}]},{"name":"European Regional Development Fund (FEDER) grants from Science and Innovation","award":["PID2019-110758RB-I00SAF2015-66015-R,"],"award-info":[{"award-number":["PID2019-110758RB-I00SAF2015-66015-R,"]}]},{"name":"European Regional Development Fund (FEDER) grants from Science and Innovation","award":["PID2023-147517OB-I00 PID2019-110758RB-I00"],"award-info":[{"award-number":["PID2023-147517OB-I00 PID2019-110758RB-I00"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["CIBERONC no. CB16\/12\/00228"],"award-info":[{"award-number":["CIBERONC no. CB16\/12\/00228"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82303057"],"award-info":[{"award-number":["82303057"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation of Hubei Province of China","award":["2023AFB521"],"award-info":[{"award-number":["2023AFB521"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:p>\n                    Fibroblast growth factor receptor 3 (\n                    <jats:italic>FGFR3<\/jats:italic>\n                    ) is one of the most frequently altered genes in bladder cancer, primarily through activating mutations that drive oncogenesis and are enriched in luminal tumors. However, the underlying gene regulatory network (GRN) remains poorly characterized. Here, we constructed an\n                    <jats:italic>FGFR3<\/jats:italic>\n                    -mutated GRN using a bottom-up bioinformatics approach, integrating transcriptomic data from bladder cancer cell lines,\n                    <jats:italic>FGFR3<\/jats:italic>\n                    -mutated tumors, and\n                    <jats:italic>FGFR3<\/jats:italic>\n                    perturbation experiments in human and mouse models. Using publicly available CRISPR\/Cas9 screening data, we identified transcription factors from this GRN that regulate the viability of\n                    <jats:italic>FGFR3<\/jats:italic>\n                    -mutated cells, with a focus on p63 (\n                    <jats:italic>TP63<\/jats:italic>\n                    ). We showed that FGFR3 activation upregulates p63 in patient-derived xenografts and cell lines, while single-cell RNA sequencing revealed heterogeneous p63 activation associated with basal differentiation. Functional studies, including\n                    <jats:italic>TP63<\/jats:italic>\n                    knockdown in FGFR3-dependent in vitro and in vivo models and RNA-seq along with p63 ChIP-seq, demonstrated that p63 directly promotes cell proliferation and migration and uncovered a positive feedback loop between FGFR3 and p63. Together, these findings support p63 as a protumorigenic regulator in\n                    <jats:italic>FGFR3-<\/jats:italic>\n                    mutated tumors despite their luminal differentiation and provide a detailed FGFR3-driven GRN, offering insights into FGFR3-induced oncogenic dependency and potential strategies to circumvent resistance to FGFR inhibitors.\n                  <\/jats:p>\n                  <jats:p>FGFR3 mutations drive bladder carcinogenesis. This study identifies a FGFR3 network, including p63, revealing oncogenic dependencies and offering insights into tumor biology and therapies<\/jats:p>","DOI":"10.1172\/jci193280","type":"journal-article","created":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T19:50:23Z","timestamp":1785700223000},"source":"Crossref","is-referenced-by-count":0,"title":["FGFR3-driven gene regulatory network analysis reveals a protumoral role for p63 in luminal bladder tumors"],"prefix":"10.1172","volume":"136","author":[{"given":"Aura","family":"Moreno-Vega","sequence":"first","affiliation":[{"name":"Institut Curie, Centre National de Recherche Scientifique (CNRS), UMR144, Molecular Oncology team, PSL Research University, Sorbonne Universit\u00e9 UPMC Universit\u00e9 Paris 6, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"Zambrano","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Medicina, Instituto de Oncolog\u00eda \u00c1ngel H. Roffo, \u00c1rea de Investigaci\u00f3n, Buenos Aires, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilia","family":"Estrada-Virrueta","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre National de Recherche Scientifique (CNRS), UMR144, Molecular Oncology team, PSL Research University, Sorbonne Universit\u00e9 UPMC Universit\u00e9 Paris 6, Paris, France."},{"name":"Universit\u00e9 de Paris-Saclay, Universit\u00e9 d\u2019Evry, Genopole, Evry, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Meng","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre National de Recherche Scientifique (CNRS), UMR144, Molecular Oncology team, PSL Research University, Sorbonne Universit\u00e9 UPMC Universit\u00e9 Paris 6, Paris, France."},{"name":"Health Science Center, Hubei Minzu University, Enshi, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Puig","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, INSERM, CHU Lille, UMR9020 \u2013 UMR-1277 - Canther, F-59000 Lille, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5660-4941","authenticated-orcid":true,"given":"Helene","family":"Neyret-Kahn","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre National de Recherche Scientifique (CNRS), UMR144, Molecular Oncology team, PSL Research University, Sorbonne Universit\u00e9 UPMC Universit\u00e9 Paris 6, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjun","family":"Shi","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre National de Recherche Scientifique (CNRS), UMR144, Molecular Oncology team, PSL Research University, Sorbonne Universit\u00e9 UPMC Universit\u00e9 Paris 6, Paris, France."},{"name":"Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2671-5576","authenticated-orcid":true,"given":"Florent","family":"Dufour","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre National de Recherche Scientifique (CNRS), UMR144, Molecular Oncology team, PSL Research University, Sorbonne Universit\u00e9 UPMC Universit\u00e9 Paris 6, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guerric","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre National de Recherche Scientifique (CNRS), UMR144, Molecular Oncology team, PSL Research University, Sorbonne Universit\u00e9 UPMC Universit\u00e9 Paris 6, Paris, France."},{"name":"Institut Curie, CNRS UMR9029, INSERM U1353, IMPACT team, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Li","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre National de Recherche Scientifique (CNRS), UMR144, Molecular Oncology team, PSL Research University, Sorbonne Universit\u00e9 UPMC Universit\u00e9 Paris 6, Paris, France."},{"name":"Institut Curie, CNRS UMR9029, INSERM U1353, IMPACT team, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarice","family":"Groeneveld","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre National de Recherche Scientifique (CNRS), UMR144, Molecular Oncology team, PSL Research University, Sorbonne Universit\u00e9 UPMC Universit\u00e9 Paris 6, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Fontugne","sequence":"additional","affiliation":[{"name":"Institut Curie, CNRS UMR9029, INSERM U1353, IMPACT team, Paris, France."},{"name":"Department of Pathology, Institut Curie, Saint-Cloud, France."},{"name":"Universit\u00e9 Versailles St-Quentin, Universit\u00e9 Paris-Saclay, F-78180, Montigny-le-Bretonneux, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"P\u00e9rez-Escavy","sequence":"additional","affiliation":[{"name":"Molecular and Translational Oncology Division, Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT); Cell and Molecular Oncology, Instituto de Investigaci\u00f3n Hospital \u201c12 de Octubre\u201d; and CIBER Cancer (CIBERONC), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wajdi","family":"Dhifli","sequence":"additional","affiliation":[{"name":"Univ. 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