Snail promotes lymph node metastasis and Twist enhances tumor deposit formation through epithelial-mesenchymal transition in colorectal cancer

Hum Pathol. 2013 Feb;44(2):173-80. doi: 10.1016/j.humpath.2012.03.029. Epub 2012 Sep 10.


Snail and Twist, transcriptional repressors of E-cadherin as well as inducers of epithelial-mesenchymal transition, play pivotal roles in tumor invasion and metastasis. We investigated the expression of Snail, Twist, and E-cadherin by immunohistochemistry in 193 colorectal cancers, including 79 with positive lymph nodes, 36 with tumor deposits, 39 with both, and 39 with no metastases. Snail was expressed to a greater extent in the group with positive lymph nodes (68.4%), whereas Twist was overexpressed in patients with other metastases (75.0%). Ectopic expression of Snail and Twist correlated with reduced membranous expression of E-cadherin. Importantly, Snail overexpression correlated significantly with lymph node metastasis (P < .0001), whereas Twist up-regulation correlated strongly with other metastases (P < .0001). Multivariate logistic regression analysis showed that Snail was an independent predictor of lymph node metastasis (odds ratio, 4.445; 95% confidence interval, 2.250-8.781; P < .0001), whereas Twist displayed predictive value for metastasis formation (odds ratio, 5.606; 95% confidence interval, 2.829-11.111; P < .0001), suggesting that lymph node and other metastases may follow different signaling pathways. In conclusion, ectopic expression of Snail and Twist contributed to lymph node and disseminated metastasis, respectively, by reducing E-cadherin expression, providing a novel role for Snail and Twist in the progression of colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Cadherins / metabolism
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / metabolism
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Snail Family Transcription Factors
  • Tissue Array Analysis
  • Transcription Factors / metabolism*
  • Twist-Related Protein 1 / metabolism*
  • Up-Regulation


  • Biomarkers, Tumor
  • Cadherins
  • Snail Family Transcription Factors
  • Transcription Factors
  • Twist-Related Protein 1