KLF4 and SOX9 transcription factors antagonize β-catenin and inhibit TCF-activity in cancer cells

Hassan Sellak, Songwei Wu, Thomas M. Lincoln

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The transcriptional activator β-catenin is a key mediator of the canonical Wnt signaling pathway. β-catenin itself does not bind DNA but functions via interaction with T-cell factor (TCF)/lymphoid-enhancing factor (LEF) transcription factors. Thus, in the case of active Wnt signaling, β-catenin, in cooperation with TCF/LEF proteins family, activates the expression of a wide variety of genes. To date, the list of established β-catenin interacting targets is far from complete. In this study, we aimed to establish the interaction between β-catenin and transcription factors that might affect TCF activity. We took advantage of EMSA, using TCF as a probe, to screen oligonucleotides known to bind specific transcription factors that might dislodge or antagonize β-catenin/TCF binding. We found that Sox9 and KLF4 antagonize β-catenin/TCF binding in HEK293, A549, SW480, and T47D cells. This inhibition of TCF binding was concentration-dependent and correlated to the in vitro TCF-luciferase functional assays. Overexpression of Sox9 and KLF4 transcription factors in cancer cells shows a concentration-dependent reduction of TCF-luciferase as well as the TCF-binding activities. In addition, we demonstrated that both Sox9 and KLF4 interact with β-catenin in an immunoprecipitation assay and reduce its binding to TCF4. Together, these results demonstrate that Sox9 and KLF4 transcription factors antagonize β-catenin/TCF in cancer cells.

Original languageEnglish (US)
Pages (from-to)1666-1675
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1823
Issue number10
DOIs
Publication statusPublished - Oct 1 2012

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Keywords

  • Cancer
  • KLF4
  • Sox9
  • T-cell factor
  • Wnt signaling
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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