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Recent studies show that AT\/RTs comprise three molecular subgroups, namely AT\/RT-TYR, AT\/RT-MYC and AT\/RT-SHH. The subgroups show distinct expression patterns of genes involved in ciliogenesis, however, little is known about the functional roles of primary cilia in the biology of AT\/RT. Here, we show that primary cilia are present across all AT\/RT subgroups with specific enrichment in AT\/RT-TYR patient samples. Furthermore, we demonstrate that primary ciliogenesis contributes to AT\/RT biology in vitro and in vivo. Specifically, we observed a significant decrease in proliferation and clonogenicity following disruption of primary ciliogenesis in AT\/RT cell line models. Additionally, apoptosis was significantly increased via the induction of STAT1 and DR5 signaling, as detected by proteogenomic profiling. In a <jats:italic>Drosophila<\/jats:italic> model of <jats:italic>SMARCB1<\/jats:italic> deficiency, concomitant knockdown of several cilia-associated genes resulted in a substantial shift of the lethal phenotype with more than 20% of flies reaching adulthood. We also found significantly extended survival in an orthotopic xenograft mouse model of AT\/RT upon disruption of primary ciliogenesis. Taken together, our findings indicate that primary ciliogenesis or its downstream signaling contributes to the aggressiveness of AT\/RT and, therefore, may constitute a novel therapeutic target.<\/jats:p>","DOI":"10.1038\/s41419-022-05243-4","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T17:02:36Z","timestamp":1663693356000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Primary cilia contribute to the aggressiveness of atypical teratoid\/rhabdoid tumors"],"prefix":"10.1038","volume":"13","author":[{"given":"Lena","family":"Bl\u00fcmel","sequence":"first","affiliation":[]},{"given":"Nan","family":"Qin","sequence":"additional","affiliation":[]},{"given":"Johannes","family":"Berlandi","sequence":"additional","affiliation":[]},{"given":"Eunice","family":"Paisana","sequence":"additional","affiliation":[]},{"given":"Rita","family":"Casc\u00e3o","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Cust\u00f3dia","sequence":"additional","affiliation":[]},{"given":"David","family":"Pauck","sequence":"additional","affiliation":[]},{"given":"Daniel","family":"Picard","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8622-3261","authenticated-orcid":false,"given":"Maike","family":"Langini","sequence":"additional","affiliation":[]},{"given":"Kai","family":"St\u00fchler","sequence":"additional","affiliation":[]},{"given":"Frauke-Dorothee","family":"Meyer","sequence":"additional","affiliation":[]},{"given":"Sarah","family":"G\u00f6bbels","sequence":"additional","affiliation":[]},{"given":"Bastian","family":"Malzkorn","sequence":"additional","affiliation":[]},{"given":"Max C.","family":"Liebau","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o T.","family":"Barata","sequence":"additional","affiliation":[]},{"given":"Astrid","family":"Jeibmann","sequence":"additional","affiliation":[]},{"given":"Kornelius","family":"Kerl","sequence":"additional","affiliation":[]},{"given":"Serap","family":"Erkek","sequence":"additional","affiliation":[]},{"given":"Marcel","family":"Kool","sequence":"additional","affiliation":[]},{"given":"Stefan M.","family":"Pfister","sequence":"additional","affiliation":[]},{"given":"Pascal D.","family":"Johann","sequence":"additional","affiliation":[]},{"given":"Michael C.","family":"Fr\u00fchwald","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-4737","authenticated-orcid":false,"given":"Arndt","family":"Borkhardt","sequence":"additional","affiliation":[]},{"given":"Guido","family":"Reifenberger","sequence":"additional","affiliation":[]},{"given":"Claudia C.","family":"Faria","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2455-2489","authenticated-orcid":false,"given":"Ute","family":"Fischer","sequence":"additional","affiliation":[]},{"given":"Martin","family":"Hasselblatt","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8737-2610","authenticated-orcid":false,"given":"Jasmin","family":"Bartl","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9404-9993","authenticated-orcid":false,"given":"Marc","family":"Remke","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"5243_CR1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3171\/jns.1996.85.1.0056","volume":"85","author":"LB Rorke","year":"1996","unstructured":"Rorke LB, Packer RJ, Biegel JA. 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