TAF4b and Jun/activating protein-1 collaborate to regulate the expression of integrin alpha6 and cancer cell migration properties

Mol Cancer Res. 2010 Apr;8(4):554-68. doi: 10.1158/1541-7786.MCR-09-0159. Epub 2010 Mar 30.

Abstract

The TAF4b subunit of the transcription factor IID, which has a central role in transcription by polymerase II, is involved in promoter recognition by selective recruitment of activators. The activating protein-1 (AP-1) family members participate in oncogenic transformation via gene regulation. Utilizing immunoprecipitation of endogenous protein complexes, we documented specific interactions between Jun family members and TATA box binding protein-associated factors (TAF) in colon HT29 adenocarcinoma cells. Particularly, TAF4b and c-Jun were found to colocalize and interact in the nucleus of advanced carcinoma cells and in cells with epithelial-to-mesenchymal transition (EMT) characteristics. TAF4b was found to specifically regulate the AP-1 target gene involved in EMT integrin alpha6, thus altering related cellular properties such as migration potential. Using a chromatin immunoprecipitation approach in colon adenocarcinoma cell lines, we further identified a synergistic role for TAF4b and c-Jun and other AP-1 family members on the promoter of integrin alpha6, underlining the existence of a specific mechanism related to gene expression control. We show evidence for the first time of an interdependence of TAF4b and AP-1 family members in cell type-specific promoter recognition and initiation of transcription in the context of cancer progression and EMT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Cell Dedifferentiation / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Integrin alpha6 / genetics*
  • Integrin alpha6 / metabolism
  • Neoplasm Invasiveness / genetics*
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Promoter Regions, Genetic / genetics
  • TATA-Binding Protein Associated Factors / genetics*
  • TATA-Binding Protein Associated Factors / metabolism
  • Transcription Factor AP-1 / genetics*
  • Transcription Factor AP-1 / metabolism
  • Transcription Factor TFIID / genetics*
  • Transcription Factor TFIID / metabolism
  • Transcriptional Activation / genetics*

Substances

  • Integrin alpha6
  • TAF4B protein, human
  • TATA-Binding Protein Associated Factors
  • Transcription Factor AP-1
  • Transcription Factor TFIID