000128941 001__ 128941
000128941 005__ 20240228143359.0
000128941 0247_ $$2doi$$a10.1158/0008-5472.CAN-16-1144
000128941 0247_ $$2pmid$$apmid:27634760
000128941 0247_ $$2ISSN$$a0008-5472
000128941 0247_ $$2ISSN$$a0099-7013
000128941 0247_ $$2ISSN$$a0099-7374
000128941 0247_ $$2ISSN$$a1538-7445
000128941 0247_ $$2altmetric$$aaltmetric:11987363
000128941 037__ $$aDKFZ-2017-04953
000128941 041__ $$aeng
000128941 082__ $$a610
000128941 1001_ $$0P:(DE-He78)063aa0f47328a6f24c7e0bcdfd258b74$$aKonotop, Gleb$$b0$$eFirst author$$udkfz
000128941 245__ $$aPharmacological Inhibition of Centrosome Clustering by Slingshot-Mediated Cofilin Activation and Actin Cortex Destabilization.
000128941 260__ $$aPhiladelphia, Pa.$$bAACR$$c2016
000128941 3367_ $$2DRIVER$$aarticle
000128941 3367_ $$2DataCite$$aOutput Types/Journal article
000128941 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1524483082_2971
000128941 3367_ $$2BibTeX$$aARTICLE
000128941 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000128941 3367_ $$00$$2EndNote$$aJournal Article
000128941 520__ $$aCentrosome amplification is a hallmark of virtually all types of cancers, including solid tumors and hematologic malignancies. Cancer cells with extra centrosomes use centrosome clustering (CC) to allow for successful division. Because normal cells do not rely on this mechanism, CC is regarded as a promising target to selectively eradicate cells harboring supernumerary centrosomes. To identify novel inhibitors of CC, we developed a cell-based high-throughput screen that reports differential drug cytotoxicity for isogenic cell populations with different centrosome contents. We identified CP-673451 and crenolanib, two chemically related compounds originally developed for the inhibition of platelet-derived growth factor receptor β (PDGFR-β), as robust inhibitors of CC with selective cytotoxicity for cells with extra centrosomes. We demonstrate that these compounds induce mitotic spindle multipolarity by activation of the actin-severing protein cofilin, leading to destabilization of the cortical actin network, and provide evidence that this activation is dependent on slingshot phosphatases 1 and 2 but unrelated to PDGFR-β inhibition. More specifically, we found that although both compounds attenuated PDGF-BB-induced signaling, they significantly enhanced the phosphorylation of PDGFR-β downstream effectors, Akt and MEK, in almost all tested cancer cell lines under physiologic conditions. In summary, our data reveal a novel mechanism of CC inhibition depending on cofilin-mediated cortical actin destabilization and identify two clinically relevant compounds interfering with this tumor cell-specific target. Cancer Res; 76(22); 6690-700. ©2016 AACR.
000128941 536__ $$0G:(DE-HGF)POF3-317$$a317 - Translational cancer research (POF3-317)$$cPOF3-317$$fPOF III$$x0
000128941 588__ $$aDataset connected to CrossRef, PubMed,
000128941 650_7 $$2NLM Chemicals$$aActins
000128941 650_7 $$2NLM Chemicals$$aCofilin 1
000128941 7001_ $$0P:(DE-He78)51d9a72bd08e54c9ae15b6c76e7e29f5$$aBausch, Elena$$b1$$udkfz
000128941 7001_ $$aNagai, Tomoaki$$b2
000128941 7001_ $$0P:(DE-He78)ecbbb1c983682c668a4df84d2901000b$$aTurchinovich, Andrey$$b3$$udkfz
000128941 7001_ $$0P:(DE-He78)ecb33fb615e08035fdcefcaebfdff8f0$$aBecker, Natalia$$b4$$udkfz
000128941 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b5$$udkfz
000128941 7001_ $$0P:(DE-He78)3c0da8e3caa2aa50cad85152aa0465ad$$aBoutros, Michael$$b6$$udkfz
000128941 7001_ $$aMizuno, Kensaku$$b7
000128941 7001_ $$0P:(DE-He78)493c5fbf69f1b20df6f048712f3ad4a0$$aKrämer, Alwin$$b8$$udkfz
000128941 7001_ $$0P:(DE-He78)1cb537e833afd985097ccfaddffb2ef3$$aRaab, Marc-Steffen$$b9$$eLast author$$udkfz
000128941 773__ $$0PERI:(DE-600)2036785-5$$a10.1158/0008-5472.CAN-16-1144$$gVol. 76, no. 22, p. 6690 - 6700$$n22$$p6690 - 6700$$tCancer research$$v76$$x1538-7445$$y2016
000128941 909CO $$ooai:inrepo02.dkfz.de:128941$$pVDB
000128941 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)063aa0f47328a6f24c7e0bcdfd258b74$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000128941 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)51d9a72bd08e54c9ae15b6c76e7e29f5$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ
000128941 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)ecbbb1c983682c668a4df84d2901000b$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000128941 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)ecb33fb615e08035fdcefcaebfdff8f0$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ
000128941 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ
000128941 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)3c0da8e3caa2aa50cad85152aa0465ad$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ
000128941 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)493c5fbf69f1b20df6f048712f3ad4a0$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000128941 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)1cb537e833afd985097ccfaddffb2ef3$$aDeutsches Krebsforschungszentrum$$b9$$kDKFZ
000128941 9131_ $$0G:(DE-HGF)POF3-317$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vTranslational cancer research$$x0
000128941 9141_ $$y2016
000128941 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000128941 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCANCER RES : 2015
000128941 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000128941 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000128941 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000128941 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000128941 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000128941 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000128941 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000128941 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000128941 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine
000128941 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000128941 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000128941 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bCANCER RES : 2015
000128941 9201_ $$0I:(DE-He78)G170-20160331$$kG170$$lExperimentelle Therapien hämatologischer Neoplasien$$x0
000128941 9201_ $$0I:(DE-He78)C080-20160331$$kC080$$lMolekulare Epidemiologie$$x1
000128941 9201_ $$0I:(DE-He78)C060-20160331$$kC060$$lBiostatistik$$x2
000128941 9201_ $$0I:(DE-He78)B110-20160331$$kB110$$lSignalwege und Funktionelle Genomik$$x3
000128941 9201_ $$0I:(DE-He78)G330-20160331$$kG330$$lKKE Molekulare Hämatologie/Onkologie$$x4
000128941 980__ $$ajournal
000128941 980__ $$aVDB
000128941 980__ $$aI:(DE-He78)G170-20160331
000128941 980__ $$aI:(DE-He78)C080-20160331
000128941 980__ $$aI:(DE-He78)C060-20160331
000128941 980__ $$aI:(DE-He78)B110-20160331
000128941 980__ $$aI:(DE-He78)G330-20160331
000128941 980__ $$aUNRESTRICTED