دورية أكاديمية
أعرض في EDS

AURKA and PLK1 inhibition selectively and synergistically block cell cycle progression in diffuse midline glioma.

التفاصيل البيبلوغرافية
العنوان: AURKA and PLK1 inhibition selectively and synergistically block cell cycle progression in diffuse midline glioma.
المؤلفون: Metselaar DS; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584CS Utrecht, the Netherlands.; Emma Children's Hospital, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Pediatric Oncology, Cancer Center Amsterdam, Amsterdam, the Netherlands., du Chatinier A; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584CS Utrecht, the Netherlands., Meel MH; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584CS Utrecht, the Netherlands., Ter Huizen G; Emma Children's Hospital, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Pediatric Oncology, Cancer Center Amsterdam, Amsterdam, the Netherlands., Waranecki P; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584CS Utrecht, the Netherlands., Goulding JR; Emma Children's Hospital, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Pediatric Oncology, Cancer Center Amsterdam, Amsterdam, the Netherlands., Bugiani M; Department of Pathology, Amstrdam University Medical Centers, Amsterdam, the Netherlands., Koster J; Department of Oncogenomics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands., Kaspers GJL; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584CS Utrecht, the Netherlands.; Emma Children's Hospital, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Pediatric Oncology, Cancer Center Amsterdam, Amsterdam, the Netherlands., Hulleman E; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584CS Utrecht, the Netherlands.
المصدر: IScience [iScience] 2022 May 13; Vol. 25 (6), pp. 104398. Date of Electronic Publication: 2022 May 13 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2018]-
مستخلص: Diffuse midline gliomas (DMG) are highly malignant incurable pediatric brain tumors. In this study, we show that Aurora kinase A (AURKA) is overexpressed in DMG and can be used as a therapeutic target. Additionally, AURKA inhibition combined with CRISPR/Cas9 screening in DMG cells, revealed polo-like kinase 1 (PLK1) as a synergistic target with AURKA. Using a panel of patient-derived DMG culture models, we demonstrate that treatment with volasertib, a clinically relevant and selective PLK1 inhibitor, synergizes with different AURKA inhibitors, supporting the CRISPR screen results. Mechanistically, our results show that combined loss of PLK1 and AURKA causes a G2/M cell cycle arrest which blocks vital parts of DNA-damage repair and induces apoptosis, solely in DMG cells. Altogether, our findings highlight the importance of AURKA and PLK1 for DMG propagation and demonstrate the potential of concurrently targeting these proteins as a therapeutic strategy for these devastating pediatric brain tumors.
Competing Interests: The authors have no conflicts of interest to declare.
(© 2022 The Author(s).)
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فهرسة مساهمة: Keywords: Biological sciences; Cancer; Cell biology; Molecular biology
تواريخ الأحداث: Date Created: 20220531 Latest Revision: 20220716
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9142558
DOI: 10.1016/j.isci.2022.104398
PMID: 35637734
قاعدة البيانات: MEDLINE
الوصف
تدمد:2589-0042
DOI:10.1016/j.isci.2022.104398