ZEB1 promotes the progression and metastasis of cervical squamous cell carcinoma via the promotion of epithelial-mesenchymal transition

Int J Clin Exp Pathol. 2015 Sep 1;8(9):11258-67. eCollection 2015.

Abstract

Objective: The process of epithelial-mesenchymal transition (EMT) clearly contributes to cancer metastasis. The aim of this study was to investigate the expression of the EMT-related transcription repressor ZEB1 and the expression of EMT-associated markers (E-cadherin, β-catenin and N-cadherin) in cervical squamous cell carcinoma. In addition, the role of ZEB1 and these EMT-associated markers in the progression and metastasis of cervical squamous cell carcinoma was explored.

Methods: The expression of ZEB1, E-cadherin, β-catenin and N-cadherin was evaluated in 81 specimens of cervical squamous cell carcinoma by immunohistochemistry; the clinicopathological significance of these markers was then analyzed.

Results: 1) Of the 81 samples, 37 cases (45.7%) were positive for ZEB1, and nuclear expression of ZEB1 in tumor cells was positively associated with the differentiation status of the tumor tissue (P < 0.05), vascular invasion (P < 0.05) and lymph node metastasis (P < 0.05). 2) The loss of E-cadherin and β-catenin expression in tumor cells and the acquisition of N-cadherin expression were positively associated with the differentiation status of the tumor tissue (P < 0.05) and with the occurrence of vascular invasion (P < 0.05). 3) A significant negative correlation was observed between ZEB1 and E-cadherin expression (Spearman = -0.636, P < 0.05) and between ZEB1 and β-catenin expression (Spearman = -0.417, P < 0.05). Moreover, a significant positive correlation was observed between ZEB1 and N-cadherin expression (Spearman = 0.557, P < 0.05).

Conclusions: These results emphasize the role of EMT in cervical squamous cell carcinoma. The upregulation of ZEB1 is associated with the abnormal expression of E-cadherin, β-catenin and N-cadherin, which might promote the progression and metastasis of cervical squamous cell carcinoma.

Keywords: E-cadherin; N-cadherin; ZEB1; cervical squamous cell carcinoma; lymph nodes metastasis; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / analysis
  • Biomarkers, Tumor / analysis*
  • Cadherins / analysis
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / secondary*
  • Disease Progression
  • Epithelial-Mesenchymal Transition*
  • Female
  • Homeodomain Proteins / analysis*
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Prognosis
  • Signal Transduction
  • Transcription Factors / analysis*
  • Up-Regulation
  • Uterine Cervical Neoplasms / chemistry*
  • Uterine Cervical Neoplasms / pathology*
  • Zinc Finger E-box-Binding Homeobox 1
  • beta Catenin / analysis

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • CDH2 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Homeodomain Proteins
  • Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • beta Catenin