{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T07:21:22Z","timestamp":1773904882862,"version":"3.50.1"},"reference-count":95,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG23341"],"award-info":[{"award-number":["IG23341"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Fondazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["24247"],"award-info":[{"award-number":["24247"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Medulloblastoma (MB) is the most frequent brain tumor in children. The standard treatment consists in surgery, followed by radiotherapy and chemotherapy. These therapies are only partially effective since many patients still die and those who survive suffer from neurological and endocrine disorders. Therefore, more effective therapies are needed. Primary microcephaly (MCPH) is a rare disorder caused by mutations in 25 different genes. Centromere-associated protein E (CENPE) heterozygous mutations cause the MCPH13 syndrome. As for other MCPH genes, CENPE is required for normal proliferation and survival of neural progenitors. Since there is evidence that MB shares many molecular features with neural progenitors, we hypothesized that CENPE could be an effective target for MB treatment. In ONS-76 and DAOY cells, CENPE knockdown induced mitotic defects and apoptosis. Moreover, CENPE depletion induced endogenous DNA damage accumulation, activating TP53 or TP73 as well as cell death signaling pathways. To consolidate CENPE as a target for MB treatment, we tested GSK923295, an allosteric inhibitor already in clinical trial for other cancer types. GSK923295, induced effects similar to CENPE depletion with higher penetrance, at low nM levels, suggesting that CENPE\u2019s inhibition could be a therapeutic strategy for MB treatment.<\/jats:p>","DOI":"10.3390\/cancers13051028","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T10:25:18Z","timestamp":1614594318000},"page":"1028","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["CENPE Inhibition Leads to Mitotic Catastrophe and DNA Damage in Medulloblastoma Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2966-9675","authenticated-orcid":false,"given":"Giorgia","family":"Iegiani","sequence":"first","affiliation":[{"name":"Neuroscience Institute Cavalieri Ottolenghi, 10043 Turin, Italy"},{"name":"Department of Neuroscience \u2018Rita Levi Montalcini\u2019, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Gai","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9367-6357","authenticated-orcid":false,"given":"Ferdinando","family":"Di Cunto","sequence":"additional","affiliation":[{"name":"Neuroscience Institute Cavalieri Ottolenghi, 10043 Turin, Italy"},{"name":"Department of Neuroscience \u2018Rita Levi Montalcini\u2019, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7735-3010","authenticated-orcid":false,"given":"Gianmarco","family":"Pallavicini","sequence":"additional","affiliation":[{"name":"Neuroscience Institute Cavalieri Ottolenghi, 10043 Turin, Italy"},{"name":"Department of Neuroscience \u2018Rita Levi Montalcini\u2019, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6734","DOI":"10.1158\/0008-5472.CAN-12-4331","article-title":"Personalizing the Treatment of Pediatric Medulloblastoma: Polo-like Kinase 1 as a Molecular Target in High-Risk Children","volume":"73","author":"Triscott","year":"2013","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3171\/2018.10.PEDS18377","article-title":"Childhood Brain Tumors: Current Management, Biological Insights, and Future Directions","volume":"23","author":"Pollack","year":"2019","journal-title":"J. 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