Transcription factor NF-kappaB signals antianoikic function of trefoil factor 3 on intestinal epithelial cells

Biochem Biophys Res Commun. 2000 Aug 11;274(3):576-82. doi: 10.1006/bbrc.2000.3176.


Transcription factor NF-kappaB has both pro-apoptotic and anti-apoptotic properties depending on the cell type. Its role in the intestinal epithelial cell has not been well elucidated. Trefoil factor 3 (TFF3) is an anti-apoptotic peptide secreted by intestinal goblet cells. Here we show that TFF3 activated NF-kappaB p50/p65 heterodimer within 1 h in IEC-18 cells (a nontransformed rat intestinal epithelial cell line). Moreover, we found that TFF3-treated IEC-18 cells are resistant to anoikis, an anchorage-related apoptosis in epithelium. In addition, the stable expression of a mutant form of the endogenous NF-kappaB inhibitor (IkappaBalpha(mut)) in IEC-18 cells results in a significant attenuation of anti-anoikic effect of TFF3. Taken together, these data indicate that (1) TFF3 is an endogenous gastrointestinal peptide with anti-anoikic property; (2) TFF3 activates NF-kappaB in enterocytes; and (3) TFF3-induced resistance to anoikis in intestinal epithelial cells is mediated by a distinct signaling cascade linked to NF-kappaB. Furthermore, our study implicates NF-kappaB as an important regulator in survival pathway of intestinal epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Line
  • Intestinal Mucosa / pathology*
  • Intestinal Mucosa / physiology*
  • Mucins*
  • Muscle Proteins*
  • NF-kappa B / physiology*
  • Peptides
  • Proteins / physiology*
  • Rats
  • Signal Transduction
  • Trefoil Factor-3


  • Mucins
  • Muscle Proteins
  • NF-kappa B
  • Peptides
  • Proteins
  • TFF3 protein, human
  • Trefoil Factor-3