Role of Smad proteins in the regulation of NF-κB by TGF-β in colon cancer cells

Ana M. Grau, Pran K. Datta, Jinghuan Zi, Sunil K. Halder, R. Daniel Beauchamp

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Nuclear factor kappa B (NF-κB) has been implicated in cancer cell survival. We explored the role of the TGF-β pathway in the regulation of NF-κB in colon cancer cells. TGF-β-1 treatment of the colon adenocarcinoma cell line FET-1, results in an early increase in IκB-α phosphorylation that precedes NF-κB nuclear translocation and DNA binding activity. Activation of the TGF-β type I receptor is required for the TGF-β-mediated activation of NF-κB. No activation of NF-κB is observed in a Smad4 null cell line, SW480, even though TGF-β does result in IκB-α phosphorylation in these cells. Smad4 restores the TGF-β-1-mediated NF-κB activation in SW480 cells. TGF-β-1 treatment fails to activate NF-κB or phosphorylate IκB-α in FET-1 cells expressing the inhibitory Smad, Smad7. Taken together, these results suggest a role for Smad4 in the transcriptional activation of NF-κB, and a direct effect of Smad 7 inhibiting IκB-α phosphorylation rather than through the well-established inhibition of Smad2/3 phosphorylation with subsequent inhibition of the TGF-β pathway.

Original languageEnglish (US)
Pages (from-to)1041-1050
Number of pages10
JournalCellular Signalling
Volume18
Issue number7
DOIs
StatePublished - Jul 1 2006

Keywords

  • Iκβ-α
  • NF-κβ
  • Smad4
  • Smad7
  • TGF-β

ASJC Scopus subject areas

  • Cell Biology

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    Grau, A. M., Datta, P. K., Zi, J., Halder, S. K., & Beauchamp, R. D. (2006). Role of Smad proteins in the regulation of NF-κB by TGF-β in colon cancer cells. Cellular Signalling, 18(7), 1041-1050. https://doi.org/10.1016/j.cellsig.2005.08.021