{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:02:40Z","timestamp":1778875360159,"version":"3.51.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2014\/20341-0\/Brazil"],"award-info":[{"award-number":["2014\/20341-0\/Brazil"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2016\/19820-6\/Brazil"],"award-info":[{"award-number":["2016\/19820-6\/Brazil"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2018\/18842-1\/Brazil"],"award-info":[{"award-number":["2018\/18842-1\/Brazil"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Erwin Schr\u00f6dinger Fellowship of the Austrian Science Fund","award":["J-4311"],"award-info":[{"award-number":["J-4311"]}]},{"name":"Pirate Ship Foundation"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 GM135262"],"award-info":[{"award-number":["R01 GM135262"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Supratentorial RELA fusion (ST-RELA) ependymomas (EPNs) are resistant tumors without an approved chemotherapeutic treatment. Unfortunately, the molecular mechanisms that lead to chemoresistance traits of ST-RELA remain elusive. The aim of this study was to assess RELA fusion-dependent signaling modules, specifically the role of the Hedgehog (Hh) pathway as a novel targetable vulnerability in ST-RELA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Gene expression was analyzed in EPN from patient cohorts, by microarray, RNA-seq, qRT-PCR, and scRNA-seq. Inhibitors against Smoothened (SMO) (Sonidegib) and Aurora kinase A (AURKA) (Alisertib) were evaluated. Protein expression, primary cilia formation, and drug effects were assessed by immunoblot, immunofluorescence, and immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hh components were selectively overexpressed in EPNs induced by the RELA fusion. Single-cell analysis showed that the Hh signature was primarily confined to undifferentiated, stem-like cell subpopulations. Sonidegib exhibited potent growth-inhibitory effects on ST-RELA cells, suggesting a key role in active Hh signaling; importantly, the effect of Sonidegib was reversed by primary cilia loss. We, thus, tested the effect of AURKA inhibition by Alisertib, to induce cilia stabilization\/reassembly. Strikingly, Alisertib rescued ciliogenesis and synergized with Sonidegib in killing ST-RELA cells. Using a xenograft model, we show that cilia loss is a mechanism for acquiring resistance to the inhibitory effect of Sonidegib. However, Alisertib fails to rescue cilia and highlights the need for other strategies to promote cilia reassembly, for treating ST-RELA tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study reveals a crucial role for the Hh pathway in ST-RELA tumor growth, and suggests that rescue of primary cilia represents a vulnerability of the ST-RELA EPNs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noac147","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T20:31:25Z","timestamp":1654029085000},"page":"185-198","source":"Crossref","is-referenced-by-count":7,"title":["Activation of Hedgehog signaling by the oncogenic RELA fusion reveals a primary cilia-dependent vulnerability in supratentorial ependymoma"],"prefix":"10.1093","volume":"25","author":[{"given":"Taciani","family":"de Almeida Magalh\u00e3es","sequence":"first","affiliation":[{"name":"Department of Genetics, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, S\u00e3o Paulo ,","place":["Brazil"]},{"name":"Department of Cell Biology, Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0005-3984","authenticated-orcid":false,"given":"Gustavo","family":"Alencastro Veiga Cruzeiro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, S\u00e3o Paulo ,","place":["Brazil"]},{"name":"Department of Pediatric Oncology, Dana-Farber Boston Children\u2019s Cancer and Blood Disorders Center , Boston, Massachusetts ,","place":["USA"]},{"name":"Broad Institute of Harvard and MIT , Cambridge, Massachusetts 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Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathew","family":"Ancliffe","sequence":"additional","affiliation":[{"name":"Brain Tumour Research Program, Telethon Kids Institute and the University of Western Australia , Nedlands, Western Australia ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keteryne","family":"Rodrigues da Silva","sequence":"additional","affiliation":[{"name":"Department of Genetics, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, S\u00e3o Paulo ,","place":["Brazil"]},{"name":"Brain Tumour Research Program, Telethon Kids Institute and the University of Western Australia , Nedlands, Western Australia 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de Paula Queiroz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Alberto Scrideli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3554-2769","authenticated-orcid":false,"given":"Raelene","family":"Endersby","sequence":"additional","affiliation":[{"name":"Brain Tumour Research Program, Telethon Kids Institute and the University of Western Australia , Nedlands, Western Australia ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariella 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