Transcription factor NF-kappaB signals antianoikic function of trefoil factor 3 on intestinal epithelial cells.
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.
Department of Pathology, Northwestern University, Chicago, Illinois, 60614, USA.
Y H
YH
Chen
Y
Y
Lu
I G
IG
De Plaen
L Y
LY
Wang
X D
XD
Tan
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D007413:Intestinal Mucosa / Q000473:pathology* / Q000502:physiology*; D009077:Mucins; D009124:Muscle Proteins; D016328:NF-kappa B / Q000502:physiology*; D010455:Peptides; D011506:Proteins / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction; D000071165:Trefoil Factor-3
D009077:Mucins; D009124:Muscle Proteins; D016328:NF-kappa B; D010455:Peptides; D011506:Proteins; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3