Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation

Gastroenterology. 2003 Feb;124(2):392-400. doi: 10.1053/gast.2003.50047.


Background & aims: Enterotoxigenic Bacteroides fragilis that secrete a zinc-dependent metalloprotease toxin termed the B. fragilis toxin (BFT) have been associated with acute diarrheal disease. BFT rapidly cleaves the extracellular domain of E-cadherin, leading to the complete degradation of the E-cadherin protein. E-cadherin is the primary intercellular adhesion protein of the zonula adherens, and its cytoplasmic domain associates with the nuclear signaling protein beta-catenin. The goal of this study was to examine if BFT triggers beta-catenin nuclear signaling in intestinal epithelial cells.

Methods: Cell biologic and biochemical techniques were combined to address beta-catenin nuclear signaling stimulated by BFT.

Results: Loss of membrane-associated E-cadherin after BFT treatment of human colonic epithelial cells (HT29/C1 clone) triggers beta-catenin nuclear localization within 3 hours. Subsequently, c-myc transcription and translation are induced and persistent cellular proliferation ensues, mediated in part by beta-catenin/T-cell factor-dependent transcriptional activation. Cellular proliferation is stimulated by as little as 5 x 10(-10) mol/L BFT.

Conclusions: To our knowledge, BFT is the first bacterial toxin reported to activate T-cell factor-dependent beta-catenin nuclear signaling in intestinal epithelial cells. These results suggest that genetic evolution of this common colonic commensal has rendered an organism with the potential to contribute to oncogenic transformation in the colon.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Toxins / pharmacology*
  • Biological Transport / drug effects
  • Cell Division / drug effects
  • Cell Nucleus / metabolism
  • Colon / cytology
  • Colon / drug effects
  • Colon / metabolism
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / metabolism
  • Enterotoxins / pharmacology*
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Metalloendopeptidases / pharmacology*
  • Protein Biosynthesis / drug effects
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Signal Transduction / physiology
  • TCF Transcription Factors
  • Tissue Distribution / drug effects
  • Trans-Activators / metabolism
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured
  • beta Catenin


  • Bacterial Toxins
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Enterotoxins
  • Proto-Oncogene Proteins c-myc
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Trans-Activators
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • beta Catenin
  • Bacteroides fragilis toxin
  • Metalloendopeptidases