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The effects of T-type calcium channel blocker mibefradil on cell growth, death and invasion were assessed with cell counting, alamar blue, trypan blue and transwell assays. Proteomic-based drug target and signaling pathway mapping was performed with Reverse Phase Protein Arrays (RPPA). Co-expression modules of single cell RNA-seq data were generated using high dimensional weighted gene co-expression network analysis (hdWGCNA). Orthotopic xenografts were used for therapeutic studies with the T-Type calcium channel blocker mibefradil.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>T-type calcium channels were upregulated in more than 30% of medulloblastoma tumors and patients with high expression associated with a worse prognosis. T-type calcium channels had variable expression across all the subgroups of medulloblastoma at the bulk RNA-seq and single-cell RNA-seq level. Mibefradil treatment or siRNA mediated silencing of T-type calcium channels inhibited tumor cell growth, viability and invasion. RPPA-based protein\/phosphoprotein signal pathway activation mapping of T-type calcium channel inhibition and single cell hdWGCNA identified altered cancer signaling pathways. Oral administration of mibefradil inhibited medulloblastoma xenograft growth and prolonged animal survival.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our results represent a first comprehensive multi-omic characterization of T-type calcium channels in medulloblastoma and provide preclinical data for repurposing mibefradil as a treatment strategy for these relatively common pediatric brain tumors.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11060-025-04967-5","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T21:27:30Z","timestamp":1739827650000},"page":"121-130","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["T-type calcium channels regulate medulloblastoma and can be targeted for therapy"],"prefix":"10.1007","volume":"173","author":[{"given":"Collin J.","family":"Dube","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shekhar","family":"Saha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulas","family":"Yener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farina","family":"Hanif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadie","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Myron K.","family":"Gibert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Marcinkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanvika","family":"Vegiraju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Sorot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa I.","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia D.","family":"Wulfkuhle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Vernon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Dell\u2019Olio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajitha","family":"Anbu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Mulcahy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Kefas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadila","family":"Guessous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel F.","family":"Petricoin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Abounader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"issue":"4","key":"4967_CR1","first-page":"353","volume":"24","author":"K Juraschka","year":"2019","unstructured":"Juraschka K, Taylor MD (2019) Medulloblastoma in the age of molecular subgroups: a review: JNSPG 75th anniversary invited Review article. 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