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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
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000127482 520__ $$aDysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as a promising biomarker for early diagnosis or unfavorable prognosis. However, the expression of KLK6 in carcinomas derived from mucosal epithelia, including head and neck squamous cell carcinoma (HNSCC), and its mode of action has not been addressed so far.Stable clones of human mucosal tumor cell lines were generated with shRNA-mediated silencing or ectopic overexpression to characterize the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with primary HNSCC samples from a retrospective patient cohort (n = 162) were stained by immunohistochemistry and the correlation between KLK6 staining and survival was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard model analysis.KLK6 expression was detected in head and neck tumor cell lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory function of KLK6 on tumor cell proliferation and mobility. FaDu clones with silenced KLK6 expression displayed molecular features resembling epithelial-to-mesenchymal transition, nuclear β-catenin accumulation and higher resistance against irradiation. Low KLK6 protein expression in primary tumors from oropharyngeal and laryngeal SCC patients was significantly correlated with poor progression-free (p = 0.001) and overall survival (p < 0.0005), and served as an independent risk factor for unfavorable clinical outcome.In summary, detection of low KLK6 expression in primary tumors represents a promising tool to stratify HNSCC patients with high risk for treatment failure. These patients might benefit from restoration of KLK6 expression or pharmacological targeting of signaling pathways implicated in EMT.
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000127482 650_7 $$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
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