KLF4, Slug and EMT in Head and Neck Squamous Cell Carcinoma

Cells. 2021 Mar 3;10(3):539. doi: 10.3390/cells10030539.

Abstract

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.

Keywords: FaDu; SCC-25; TWIST; TissueFaxs; UPCI-SCC090; ZEB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Humans
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics*
  • Kruppel-Like Transcription Factors / metabolism
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Signal Transduction
  • Snail Family Transcription Factors / genetics*
  • Snail Family Transcription Factors / metabolism
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Survival Analysis
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Twist-Related Protein 1 / genetics*
  • Twist-Related Protein 1 / metabolism
  • Vimentin / genetics
  • Vimentin / metabolism
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Nuclear Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TGFB1 protein, human
  • TWIST1 protein, human
  • Transforming Growth Factor beta1
  • Tumor Suppressor Protein p53
  • Twist-Related Protein 1
  • VIM protein, human
  • Vimentin
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1