000181681 001__ 181681 000181681 005__ 20241220120851.0 000181681 0247_ $$2doi$$a10.1002/ijc.34250 000181681 0247_ $$2pmid$$apmid:36094276 000181681 0247_ $$2ISSN$$a0020-7136 000181681 0247_ $$2ISSN$$a1097-0215 000181681 0247_ $$2altmetric$$aaltmetric:135832647 000181681 037__ $$aDKFZ-2022-02161 000181681 041__ $$aEnglish 000181681 082__ $$a610 000181681 1001_ $$0P:(DE-He78)a48f07bcd002effe04d0fd59fa8e3340$$aFrensemeier, Kristin$$b0$$eFirst author$$udkfz 000181681 245__ $$aDickkopf-1 expression is repressed by oncogenic human papillomaviruses (HPVs) and regulates the Cisplatin sensitivity of HPV-positive cancer cells in a JNK-dependent manner. 000181681 260__ $$aBognor Regis$$bWiley-Liss$$c2022 000181681 3367_ $$2DRIVER$$aarticle 000181681 3367_ $$2DataCite$$aOutput Types/Journal article 000181681 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1666685267_11980 000181681 3367_ $$2BibTeX$$aARTICLE 000181681 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000181681 3367_ $$00$$2EndNote$$aJournal Article 000181681 500__ $$a#EA:F065#LA:F065# / 2022 Dec 15;151(12):2215-2228 000181681 520__ $$aOncogenic human papillomavirus (HPV) types control the phenotype of cervical cancer cells through the sustained expression of the viral E6/E7 oncogenes. Here, we show that they strongly restrain expression of the putative tumor suppressor protein Dkk1 (Dickkopf-1) in HPV-positive cervical cancer cells through the restriction of p53 expression by the continuously expressed endogenous E6 oncoprotein. Moreover, our study reveals that compromised Dkk1 expression is linked to increased resistance of HPV-positive cervical cancer cells toward the proapoptotic activity of Cisplatin. Although Dkk1 can act as a Wnt antagonist, the antiapoptotic effect resulting from Dkk1 repression is not linked to an activation of this pathway. Rather, transcriptome and functional analyses uncover that Dkk1 repression leads to a strongly diminished stimulation of c-Jun N-terminal kinase (JNK) signaling which is required for efficient apoptosis induction by Cisplatin in cervical cancer cells. Further, we observed that Dkk1-depleted cervical cancer cells induce senescence under Cisplatin treatment instead of apoptosis, suggesting that Dkk1 levels can strongly influence the phenotypic response of these cells toward Cisplatin. Collectively, these results provide new insights into the virus/host cell crosstalk in cervical cancer cells by identifying Dkk1 as a cellular target which is maintained under strong negative control by the continuous expression of the HPV oncogenes. Moreover, they identify Dkk1 as a critical determinant for the sensitivity of cervical cancer cells toward Cisplatin, showing that Dkk1 repression leads to increased Cisplatin resistance by impairing proapoptotic JNK signaling. 000181681 536__ $$0G:(DE-HGF)POF4-316$$a316 - Infektionen, Entzündung und Krebs (POF4-316)$$cPOF4-316$$fPOF IV$$x0 000181681 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000181681 650_7 $$2Other$$aCisplatin 000181681 650_7 $$2Other$$aDickkopf-1 000181681 650_7 $$2Other$$ac-Jun N-terminal kinase 000181681 650_7 $$2Other$$acervical cancer 000181681 650_7 $$2Other$$ahuman papillomavirus 000181681 7001_ $$0P:(DE-He78)36388794be2cf5f298978498ff3c64a2$$aHolzer, Angela$$b1$$udkfz 000181681 7001_ $$0P:(DE-He78)97468f1980416a4376b44e701d25f24b$$aHoppe-Seyler, Karin$$b2$$udkfz 000181681 7001_ $$0P:(DE-He78)25779f8829ab7a7650e85a4cc871e6ac$$aHoppe-Seyler, Felix$$b3$$eLast author$$udkfz 000181681 773__ $$0PERI:(DE-600)1474822-8$$a10.1002/ijc.34250$$gp. ijc.34250$$n12$$p2215-2228$$tInternational journal of cancer$$v151$$x0020-7136$$y2022 000181681 8767_ $$82022 (V10366)$$92022-06-23$$d2024-12-19$$eHybrid-OA$$jZahlung erfolgt 000181681 909CO $$ooai:inrepo02.dkfz.de:181681$$pVDB$$pOpenAPC$$popenCost 000181681 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a48f07bcd002effe04d0fd59fa8e3340$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ 000181681 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)36388794be2cf5f298978498ff3c64a2$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ 000181681 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)97468f1980416a4376b44e701d25f24b$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ 000181681 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)25779f8829ab7a7650e85a4cc871e6ac$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ 000181681 9131_ $$0G:(DE-HGF)POF4-316$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vInfektionen, Entzündung und Krebs$$x0 000181681 9141_ $$y2022 000181681 915__ $$0StatID:(DE-HGF)3001$$2StatID$$aDEAL Wiley$$d2021-02-04$$wger 000181681 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-02-04 000181681 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-02-04 000181681 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-02-04 000181681 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2022-11-25$$wger 000181681 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-25 000181681 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-25 000181681 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-25 000181681 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-25 000181681 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-25 000181681 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-25 000181681 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bINT J CANCER : 2021$$d2022-11-25 000181681 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bINT J CANCER : 2021$$d2022-11-25 000181681 915pc $$0PC:(DE-HGF)0000$$2APC$$aAPC keys set 000181681 915pc $$0PC:(DE-HGF)0001$$2APC$$aLocal Funding 000181681 9202_ $$0I:(DE-He78)F065-20160331$$kF065$$lF065 Molek. 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