KLF4, Slug and EMT in Head and Neck Squamous Cell Carcinoma
Julia Ingruber,
Dragana Savic,
Teresa Bernadette Steinbichler,
Susanne Sprung,
Felix Fleischer,
Rudolf Glueckert,
Gabriele Schweigl,
Ira-Ida Skvortsova,
Herbert Riechelmann,
József Dudás
Affiliations
Julia Ingruber
Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Innsbruck, University Hospital of Tyrol, A-6020 Innsbruck, Austria
Dragana Savic
Laboratory for Experimental and Translational Research on Radiation Oncology (EXTRO-Lab), Department of Therapeutic Radiology and Oncology, Medical University of Innsbruck, A-6020 Innsbruck, Austria
Teresa Bernadette Steinbichler
Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Innsbruck, University Hospital of Tyrol, A-6020 Innsbruck, Austria
Susanne Sprung
Department of Pathology, Medical University of Innsbruck, A-6020 Innsbruck, Austria
Felix Fleischer
Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Innsbruck, University Hospital of Tyrol, A-6020 Innsbruck, Austria
Rudolf Glueckert
Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Innsbruck, University Hospital of Tyrol, A-6020 Innsbruck, Austria
Gabriele Schweigl
Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Innsbruck, University Hospital of Tyrol, A-6020 Innsbruck, Austria
Ira-Ida Skvortsova
Laboratory for Experimental and Translational Research on Radiation Oncology (EXTRO-Lab), Department of Therapeutic Radiology and Oncology, Medical University of Innsbruck, A-6020 Innsbruck, Austria
Herbert Riechelmann
Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Innsbruck, University Hospital of Tyrol, A-6020 Innsbruck, Austria
József Dudás
Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Innsbruck, University Hospital of Tyrol, A-6020 Innsbruck, Austria
Epithelial to mesenchymal transition (EMT) is clinically relevant in head and neck squamous cell carcinoma (HNSCC). We hypothesized that EMT-transcription factors (EMT-TFs) and an anti-EMT factor, Krüppel-like-factor-4 (KLF4) regulate EMT in HNSCC. Ten control mucosa and 37 HNSCC tissue samples and three HNSCC cell lines were included for investigation of EMT-TFs, KLF4 and vimentin at mRNA and protein levels. Slug gene expression was significantly higher, whereas, KLF4 gene expression was significantly lower in HNSCC than in normal mucosa. In the majority of HNSCC samples, there was a significant negative correlation between KLF4 and Slug gene expression. Slug gene expression was significantly higher in human papilloma virus (HPV) negative HNSCC, and in tumor samples with irregular p53 gene sequence. Transforming-growth-factor-beta-1 (TGF- β1) contributed to downregulation of KLF4 and upregulation of Slug. Two possible regulatory pathways could be suggested: (1) EMT-factors induced pathway, where TGF-β1 induced Slug together with vimentin, and KLF4 was down regulated at the same time; (2) p53 mutations contributed to upregulation and stabilization of Slug, where also KLF4 could co-exist with EMT-TFs.
