ArticleMolecular cancer2015
Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 59 citations in OpenAlex.
- Epithelial to mesenchymal transition and HPV infection in squamous cell oropharyngeal carcinomas: the papillophar study.British journal of cancer · 2017Trial
- The Kallikrein-Kinin System: Proteolytic Orchestrators of Tissue Barrier Disruption in Inflammation and Cancer.International journal of molecular sciences · 2026Review
- Downregulation of SPINK5 promotes laryngeal cancer cell malignancy through activation of KLK6-dependent glycolysis.BMC cancer · 2026Article
- Article
- AugGCL: Multimodal graph learning for spatial transcriptomics analysis with enhanced gene and morphological data.PLoS computational biology · 2026Article
- HSP90α and KLK6 Co-Regulate Stress-Induced Prostate Cancer Cell Motility.bioRxiv : the preprint server for biology · 2025Article
- Clinical correlation of p16 expression with lymphatic invasion and epithelial-mesenchymal transition (EMT) in oropharyngeal carcinomas.F1000Research · 2025Article
- Cellograph: a semi-supervised approach to analyzing multi-condition single-cell RNA-sequencing data using graph neural networks.BMC bioinformatics · 2024Article
- Intratumoral Heterogeneity in Lung Cancer.Cancers · 2023Review
- A KLK6 Activity-Based Probe Reveals a Role for KLK6 Activity in Pancreatic Cancer Cell Invasion.Journal of the American Chemical Society · 2022Article
- Remodelling of the tumour microenvironment by the kallikrein-related peptidases.Nature reviews. Cancer · 2022Review
- Article
- KLK6 Functions as an Oncogene and Unfavorable Prognostic Factor in Bladder Urothelial Carcinoma.Disease markers · 2022Article
- KLK6 mediates stemness and metabolism of gastric carcinoma cells via the PI3K/AKT/mTOR signaling pathway.Oncology letters · 2021Article
- Recent progress of biomarkers in oral cancers.Journal of the Chinese Medical Association : JCMA · 2021Article
- Epithelial-to-Mesenchymal Transition-Derived Heterogeneity in Head and Neck Squamous Cell Carcinomas.Cancers · 2021Review
- CTHRC1 expression is a novel shared diagnostic and prognostic biomarker of survival in six different human cancer subtypes.Scientific reports · 2021Article
- Kallikrein-Related Peptidase 6 Is Associated with the Tumour Microenvironment of Pancreatic Ductal Adenocarcinoma.Cancers · 2021Article
- Silencing of kallikrein-related peptidase 6 attenuates the proliferation, migration, and invasion of gastric cancer cells through inhibition of epithelial-mesenchymal transition.Experimental and therapeutic medicine · 2021Article
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9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDysregulated 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.
methodsStable 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.
resultsKLK6 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.
conclusionsIn 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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