KLF6 inhibited oral cancer migration and invasion via downregulation of mesenchymal markers and inhibition of MMP-9 activities

Int J Med Sci. 2017 Apr 9;14(6):530-535. doi: 10.7150/ijms.19024. eCollection 2017.

Abstract

Krüppel-like factors can bind to specific DNA motifs and regulate various cellular functions, such as metabolism, cell proliferation, and differentiation. Krüppel-like factor 6 (KLF6), a member of this family, is downregulated in human cancers. Oral cancer is a highly prevalent type in Taiwan. Although KLF6 overexpression in human cancer cells inhibits cell proliferation, induces apoptosis, and attenuates cell migration, the effects of KLF6 on oral cancer remains poorly elucidated. This study investigated the role of KLF6 in oral cancer tumorigenesis. Immunohistochemical staining revealed that nuclear KLF6 level was significantly and inversely associated with tumor size and stages. KLF6 overexpression attenuated the migration and invasion of oral cancer SAS cells. Zymography assay demonstrated that KLF6 inhibited the activities of matrix metalloproteinase 9 (MMP-9) and weakened the expression of mesenchymal markers, such as snail, slug, and vimentin. Our study is the first to provide demonstrate that KLF6 functions as a tumor suppressor gene and prevents the metastasis of oral cancer cells.

Keywords: kruppel-like factor 6 (KLF6); matrix metalloproteinase 9.; migration; oral cancer.

MeSH terms

  • Aged
  • Apoptosis / drug effects
  • Cell Differentiation / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Factor 6 / antagonists & inhibitors
  • Kruppel-Like Factor 6 / genetics*
  • Male
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase Inhibitors / administration & dosage*
  • Middle Aged
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness / genetics
  • Signal Transduction / drug effects

Substances

  • KLF6 protein, human
  • Kruppel-Like Factor 6
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinase 9