000127482 001__ 127482 000127482 005__ 20240228140930.0 000127482 0247_ $$2doi$$a10.1186/s12943-015-0381-6 000127482 0247_ $$2pmid$$apmid:25990935 000127482 0247_ $$2pmc$$apmc:PMC4437453 000127482 0247_ $$2altmetric$$aaltmetric:4040088 000127482 037__ $$aDKFZ-2017-03505 000127482 041__ $$aeng 000127482 082__ $$a610 000127482 1001_ $$0P:(DE-HGF)0$$aSchrader, Carola H$$b0$$eFirst author 000127482 245__ $$aKallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients. 000127482 260__ $$aLondon$$bBiomed Central$$c2015 000127482 3367_ $$2DRIVER$$aarticle 000127482 3367_ $$2DataCite$$aOutput Types/Journal article 000127482 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1524135660_24105 000127482 3367_ $$2BibTeX$$aARTICLE 000127482 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000127482 3367_ $$00$$2EndNote$$aJournal Article 000127482 520__ $$aDysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as a promising biomarker for early diagnosis or unfavorable prognosis. However, the expression of KLK6 in carcinomas derived from mucosal epithelia, including head and neck squamous cell carcinoma (HNSCC), and its mode of action has not been addressed so far.Stable clones of human mucosal tumor cell lines were generated with shRNA-mediated silencing or ectopic overexpression to characterize the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with primary HNSCC samples from a retrospective patient cohort (n = 162) were stained by immunohistochemistry and the correlation between KLK6 staining and survival was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard model analysis.KLK6 expression was detected in head and neck tumor cell lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory function of KLK6 on tumor cell proliferation and mobility. FaDu clones with silenced KLK6 expression displayed molecular features resembling epithelial-to-mesenchymal transition, nuclear β-catenin accumulation and higher resistance against irradiation. Low KLK6 protein expression in primary tumors from oropharyngeal and laryngeal SCC patients was significantly correlated with poor progression-free (p = 0.001) and overall survival (p < 0.0005), and served as an independent risk factor for unfavorable clinical outcome.In summary, detection of low KLK6 expression in primary tumors represents a promising tool to stratify HNSCC patients with high risk for treatment failure. These patients might benefit from restoration of KLK6 expression or pharmacological targeting of signaling pathways implicated in EMT. 000127482 536__ $$0G:(DE-HGF)POF3-317$$a317 - Translational cancer research (POF3-317)$$cPOF3-317$$fPOF III$$x0 000127482 588__ $$aDataset connected to CrossRef, PubMed, 000127482 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor 000127482 650_7 $$2NLM Chemicals$$abeta Catenin 000127482 650_7 $$0EC 3.4.21.-$$2NLM Chemicals$$aKLK6 protein, human 000127482 650_7 $$0EC 3.4.21.-$$2NLM Chemicals$$aKallikreins 000127482 7001_ $$aKolb, Markus$$b1 000127482 7001_ $$aZaoui, Karim$$b2 000127482 7001_ $$aFlechtenmacher, Christa$$b3 000127482 7001_ $$0P:(DE-HGF)0$$aGrabe, Niels$$b4 000127482 7001_ $$aWeber, Klaus-Josef$$b5 000127482 7001_ $$0P:(DE-He78)743a4a82daab55306a2c88b9f6bf8c2f$$aHielscher, Thomas$$b6$$udkfz 000127482 7001_ $$aPlinkert, Peter K$$b7 000127482 7001_ $$0P:(DE-He78)2e5f34f1c58eda4787a14c9dc139ca5f$$aHess, Jochen$$b8$$eLast author$$udkfz 000127482 773__ $$0PERI:(DE-600)2091373-4$$a10.1186/s12943-015-0381-6$$gVol. 14, no. 1, p. 107$$n1$$p107$$tMolecular cancer$$v14$$x1476-4598$$y2015 000127482 909CO $$ooai:inrepo02.dkfz.de:127482$$pVDB 000127482 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ 000127482 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ 000127482 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)743a4a82daab55306a2c88b9f6bf8c2f$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ 000127482 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)2e5f34f1c58eda4787a14c9dc139ca5f$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ 000127482 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 000127482 9141_ $$y2015 000127482 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bMOL CANCER : 2015 000127482 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000127482 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000127482 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000127482 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal 000127482 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ 000127482 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ 000127482 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search 000127482 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC 000127482 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000127482 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000127482 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000127482 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000127482 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000127482 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bMOL CANCER : 2015 000127482 9201_ $$0I:(DE-He78)C060-20160331$$kC060$$lBiostatistik$$x0 000127482 9201_ $$0I:(DE-He78)G405-20160331$$kG405$$lMolekulare Grundlagen von HNO-Tumoren$$x1 000127482 9201_ $$0I:(DE-He78)V964-20160331$$kV964$$lNCT-KliHD$$x2 000127482 9201_ $$0I:(DE-He78)D120-20160331$$kD120$$lAngewandte Tumor-Immunität$$x3 000127482 980__ $$ajournal 000127482 980__ $$aVDB 000127482 980__ $$aI:(DE-He78)C060-20160331 000127482 980__ $$aI:(DE-He78)G405-20160331 000127482 980__ $$aI:(DE-He78)V964-20160331 000127482 980__ $$aI:(DE-He78)D120-20160331 000127482 980__ $$aUNRESTRICTED