eprintid: 19470
rev_number: 20
eprint_status: archive
userid: 1589
dir: disk0/00/01/94/70
datestamp: 2016-01-18 12:45:46
lastmod: 2024-03-06 04:50:39
status_changed: 2016-01-18 12:45:46
type: article
metadata_visibility: show
creators_name: Schrader, Carola H.
creators_name: Kolb, Markus
creators_name: Zaoui, Karim
creators_name: Flechtenmacher, Christa
creators_name: Grabe, Niels
creators_name: Weber, Klaus-Josef
creators_name: Hielscher, Thomas
creators_name: Plinkert, Peter K.
creators_name: Hess, Jochen
title: Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients
subjects: ddc-610
divisions: i-716000
divisions: i-850300
divisions: i-911000
divisions: i-911400
divisions: i-912000
abstract: Background: Dysregulated 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.   Methods: 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.   Results: 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.   Conclusions: 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.  
date: 2015
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 1656458276
own_urn: urn:nbn:de:bsz:16-heidok-194704
language: eng
bibsort: SCHRADERCAKALLIKREIN2015
full_text_status: public
publication: Molecular cancer
volume: 14
number: 107
place_of_pub: London
pagerange: 1-14
issn: 1476-4598
citation:   Schrader, Carola H. ; Kolb, Markus ; Zaoui, Karim ; Flechtenmacher, Christa ; Grabe, Niels ; Weber, Klaus-Josef ; Hielscher, Thomas ; Plinkert, Peter K. ; Hess, Jochen  (2015) Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients.  Molecular cancer, 14 (107).  pp. 1-14.  ISSN 1476-4598     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/19470/1/12943_2015_Article_381.pdf