Role of DeltaNp63gamma in epithelial to mesenchymal transition

Jaime Lindsay, Simon S McDade, Adam Pickard, Karen D McCloskey, Dennis J McCance

Research output: Contribution to journalArticlepeer-review

Abstract

Although members of the p63 family of transcription factors are known for their role in the development and differentiation of epithelial surfaces, their function in cancer is less clear. Here, we show that depletion of the ΔNp63α and β isoforms, leaving only ΔNp63γ, results in epithelial to mesenchymal transition (EMT) in the normal breast cell line MCF10A. EMT can be rescued by the expression of the ΔNp63α isoform. We also show that ΔNp63γ expressed in a background where all the other ΔNp63 are knocked down causes EMT with an increase in TGFβ-1, -2, and -3 and downstream effectors Smads2/3/4. In addition, a p63 binding site in intron 1 of TGFβ was identified. Inhibition of the TGFβ response with a specific inhibitor results in reversion of EMT in ΔNp63α- and β-depleted cells. In summary, we show that p63 is involved in inhibiting EMT and reduction of certain p63 isoforms may be important in the development of epithelial cancers.

Original languageEnglish
Pages (from-to)3915-24
Number of pages10
JournalThe Journal of biological chemistry
Volume286
Issue number5
DOIs
Publication statusPublished - 4 Feb 2011

Keywords

  • Binding Sites
  • Breast Neoplasms
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms, Glandular and Epithelial
  • Protein Isoforms
  • Smad Proteins
  • Trans-Activators
  • Transcription Factors
  • Transforming Growth Factor beta
  • Tumor Suppressor Proteins
  • Up-Regulation
  • Journal Article
  • Research Support, Non-U.S. Gov't

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