Negative regulation of the tight junction protein tricellulin by snail-induced epithelial-mesenchymal transition in gastric carcinoma cells

Pathobiology. 2010;77(2):106-13. doi: 10.1159/000278293. Epub 2010 Mar 22.

Abstract

Objective: Tricellulin plays a central role in the sealing of epithelia at tricellular contacts. We examined the effects of Snail, an epithelial-mesenchymal transition (EMT)-related transcription factor, on the regulation of tricellulin expression in human gastric carcinoma (GC)-derived cells.

Method: Six human GC-derived cell lines were used in this study. Expression and localization of tricellulin was analyzed by reverse transcription (RT)-PCR and immunohistochemistry. Also, a Snail expression vector was transfected into HSC-45 cells to examine altered mRNA levels of tricellulin,E-cadherin, vimentin, N-cadherin and several EMT transcription factors by quantitative real-time RT-PCR.

Results: Abundant tricellulin expression was detected in all GC-derived cells examined. In HSC-45 cells, transduction of Snail decreased the expression levels of tricellulin and E-cadherin but increased vimentin and N-cadherin, which was accompanied by induction of EMT transcription factors such as Twist1, Twist2 and Slug. In normal gastric mucosa, tricellulin protein was localized at the tricellular tight junction; however, in HSC-45 cells, tricellulin protein was distributed in the cytoplasm. In GC tissues, tricellulin expression at the cellular membrane was retained in a subset of EMT-negative GCs, and it disappeared in EMT-positive GCs.

Conclusions: The findings in the present study suggest that repression of tricellulin expression may be related to Snail-induced EMT in human GCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Biomarkers, Tumor / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MARVEL Domain Containing 2 Protein
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Snail Family Transcription Factors
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Tight Junctions / genetics
  • Tight Junctions / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH2 protein, human
  • Cadherins
  • MARVEL Domain Containing 2 Protein
  • MARVELD2 protein, human
  • Membrane Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors
  • Vimentin