000181116 001__ 181116
000181116 005__ 20240301130850.0
000181116 0247_ $$2doi$$a10.18632/oncotarget.21932
000181116 0247_ $$2pmid$$apmid:29228610
000181116 0247_ $$2pmc$$apmc:PMC5722562
000181116 037__ $$aDKFZ-2022-01785
000181116 041__ $$aEnglish
000181116 082__ $$a610
000181116 1001_ $$aAlimova, Irina$$b0
000181116 245__ $$aTargeting Polo-like kinase 1 in SMARCB1 deleted atypical teratoid rhabdoid tumor.
000181116 260__ $$a[S.l.]$$bImpact Journals LLC$$c2017
000181116 3367_ $$2DRIVER$$aarticle
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000181116 3367_ $$2BibTeX$$aARTICLE
000181116 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000181116 3367_ $$00$$2EndNote$$aJournal Article
000181116 520__ $$aAtypical teratoid rhabdoid tumor (ATRT) is an aggressive and malignant pediatric brain tumor. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and essential for mitosis. Overexpression of PLK1 promotes chromosome instability and aneuploidy by overriding the G2-M DNA damage and spindle checkpoints. Recent studies suggest that targeting PLK1 by small molecule inhibitors is a promising approach to tumor therapy. We investigated the effect of PLK1 inhibition in ATRT. Gene expression analysis showed that PLK1 was overexpressed in ATRT patient samples and tumor cell lines. Genetic inhibition of PLK1 with shRNA potently suppressed ATRT cell growth in vitro. Treatment with the PLK1 inhibitor BI 6727 (Volasertib) significantly decreased cell growth, inhibited clonogenic potential, and induced apoptosis. BI6727 treatment led to G2-M phase arrest, consistent with PLK1's role as a critical regulator of mitosis. Moreover, inhibition of PLK1 by BI6727 suppressed the tumor-sphere formation of ATRT cells. Treatment also significantly decreased levels of the DNA damage proteins Ku80 and RAD51 and increased γ-H2AX expression, indicating that BI 6727 can induce DNA damage. Importantly, BI6727 significantly enhanced radiation sensitivity of ATRT cells. In vivo, BI6727 slowed growth of ATRT tumors and prolonged survival in a xenograft model. PLK1 inhibition is a compelling new therapeutic approach for treating ATRT, and the use of BI6727 should be evaluated in clinical studies.
000181116 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0
000181116 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000181116 650_7 $$2Other$$aATRT
000181116 650_7 $$2Other$$aPolo-like kinase 1
000181116 650_7 $$2Other$$aSMARCB1
000181116 650_7 $$2Other$$avolasertib
000181116 7001_ $$aPierce, Angela M$$b1
000181116 7001_ $$aHarris, Peter$$b2
000181116 7001_ $$aDonson, Andrew$$b3
000181116 7001_ $$aBirks, Diane K$$b4
000181116 7001_ $$aPrince, Eric$$b5
000181116 7001_ $$aBalakrishnan, Ilango$$b6
000181116 7001_ $$aForeman, Nicholas K$$b7
000181116 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b8$$udkfz
000181116 7001_ $$aHoffman, Lindsey$$b9
000181116 7001_ $$aVenkataraman, Sujatha$$b10
000181116 7001_ $$aVibhakar, Rajeev$$b11
000181116 773__ $$0PERI:(DE-600)2560162-3$$a10.18632/oncotarget.21932$$gVol. 8, no. 57, p. 97290 - 97303$$n57$$p97290 - 97303$$tOncoTarget$$v8$$x1949-2553$$y2017
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000181116 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000181116 9131_ $$0G:(DE-HGF)POF3-312$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunctional and structural genomics$$x0
000181116 9141_ $$y2017
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