Tip60 regulates MT1-MMP transcription and invasion of glioblastoma cells through NF-κB pathway

Clin Exp Metastasis. 2016 Jan;33(1):45-52. doi: 10.1007/s10585-015-9756-8.


A histone acetyltransferase Tat-interacting protein 60 kDa (Tip60) regulates the DNA damage response by acetylating histone and remodeling chromatin. In addition to histone acetyltransferase activity, Tip60 is known to regulate a variety of cellular functions, including gene expression, DNA damage response, cell migration and apoptosis. Lower expression of Tip60 is observed in lymphomas, melanomas, breast, colon, and lung cancer. It is widely accepted that Tip60 functions as a tumor suppressor. However, a role of Tip60 in gliomas still remains unclear. In this study, we investigated the role of Tip60 in the malignant behavior of human gliomas. By quantitative RT-PCR analysis using fresh human brain tumor tissues from 55 patients, we found that lower Tip60 expression and higher membrane-type 1 matrix metalloproteinase (MT1-MMP) expression are associated with advanced tumor grade in glioma tissues. Knockdown of Tip60 in glioblastoma cells promoted cell adhesion, spreading and MT1-MMP transcription and thereby invasion, which was suppressed by inhibition of MT1-MMP and nuclear factor-kappa B (NF-κB) activity. We demonstrate for the first time that tumor suppressor Tip60 down-regulates cell adhesion and MT1-MMP expression and thereby invasion of glioblastoma cells by suppressing NF-κB pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / pathology*
  • Cell Adhesion / genetics
  • Cell Movement / genetics
  • Down-Regulation
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic / physiology*
  • Gene Knockdown Techniques
  • Glioblastoma / pathology*
  • Histone Acetyltransferases / biosynthesis*
  • Histone Acetyltransferases / genetics
  • Humans
  • Immunoblotting
  • Lysine Acetyltransferase 5
  • Matrix Metalloproteinase 14 / biosynthesis*
  • Matrix Metalloproteinase 14 / genetics
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA, Small Interfering
  • Real-Time Polymerase Chain Reaction
  • Transcription, Genetic


  • NF-kappa B
  • RNA, Small Interfering
  • Histone Acetyltransferases
  • KAT5 protein, human
  • Lysine Acetyltransferase 5
  • MMP14 protein, human
  • Matrix Metalloproteinase 14