Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin

J Pathol. 2007 Apr;211(5):507-515. doi: 10.1002/path.2138.


Epithelial-mesenchymal transition (EMT) involving down-regulation of E-cadherin is known to play an important role in tumour progression. The aim of our study was to investigate the mRNA expression of two EMT regulators-Slug and E12/E47-in primary human gastric carcinomas and to compare this with the expression of E-cadherin and other EMT regulators (Snail, Twist, and SIP1). We studied a series of 59 gastric carcinomas by real-time quantitative RT-PCR in formalin-fixed and paraffin-embedded tissues. Thirty-four cases (58%) showed Slug up-regulation in the tumour; reduced or negative expression of E-cadherin was present in 24 of these (71%, p<0.0001). Twenty-one cases (36%) showed E12/E47 up-regulation that was not significantly associated with E-cadherin down-regulation (p=0.5734). Slug up-regulation accompanied by E-cadherin down-regulation correlated with the presence of distant metastases (p=0.0029) and with advanced pTNM stages (p=0.0424). A statistically significant association was found between Slug up-regulation and the expression of SIP1 in intestinal (p=0.0014) and Snail in diffuse (p=0.0067) carcinomas. We present the first study integrating the analysis of several EMT regulators in primary gastric carcinomas and conclude that Slug up-regulation is associated with E-cadherin down-regulation in diffuse and intestinal-type gastric carcinoma, and that this effect could be complemented by the presence of other EMT regulators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / genetics*
  • Cell Transformation, Neoplastic / genetics
  • Down-Regulation / genetics
  • Drug Synergism
  • Epithelium / physiopathology
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics
  • Neoplasm Proteins / genetics*
  • Nerve Tissue Proteins / genetics*
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • RNA-Binding Proteins / genetics*
  • Snail Family Transcription Factors
  • Stomach Neoplasms / genetics*
  • TCF Transcription Factors / genetics
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors / genetics*
  • Up-Regulation / genetics
  • Zinc Fingers / genetics


  • Cadherins
  • GEMIN2 protein, human
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • RNA-Binding Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TCF Transcription Factors
  • TCF7L1 protein, human
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors