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Transcriptional repressor snail and progression of human hepatocellular carcinoma

Keishi Sugimachi1, Shinji Tanaka, Toshifumi Kameyama

  • 1Departments of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 12, 2003
PubMed
Abstract

Insights

Snail protein, a key factor in cell adhesion, drives hepatocellular carcinoma (HCC) invasion by down-regulating E-cadherin. This study confirms Snail

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Snail protein is a transcriptional repressor of E-cadherin, a protein crucial for cell-to-cell adhesion.
  • Dysregulation of E-cadherin is implicated in tumor progression and metastasis in various cancers.
  • The role of Snail and its family member Slug in hepatocellular carcinoma (HCC) requires further elucidation.

Purpose of the Study:

  • To investigate the expression and functional role of Snail and Slug in human hepatocellular carcinoma (HCC).
  • To determine the correlation between Snail/Slug expression, E-cadherin levels, and clinicopathological features in HCC.
  • To identify the specific contribution of Snail to HCC tumor progression and invasiveness.

Main Methods:

  • Snail cDNA transfection in HCC cells (Li-7) to assess E-cadherin expression.
  • In situ hybridization and real-time reverse transcriptase-PCR to quantify Snail and Slug mRNA in 43 HCC tissue samples.
  • Immunohistochemistry to evaluate E-cadherin protein expression.
  • Correlation analysis between Snail/Slug mRNA levels, E-cadherin expression, and clinicopathological factors.

Main Results:

  • Snail cDNA transfection induced loss of E-cadherin protein expression in HCC cells.
  • Snail mRNA was predominantly expressed in HCC cells, not in surrounding non-cancerous tissues or other cell types.
  • Snail mRNA overexpression was observed in 16% of HCC cases and significantly correlated with down-regulated E-cadherin protein expression (P = 0.04).
  • The ratio of Snail mRNA in tumor versus non-tumor tissue independently correlated with tumor invasiveness (P = 0.04).
  • Slug mRNA expression did not correlate with E-cadherin levels or tumor invasiveness.

Conclusions:

  • Snail plays a significant role in human HCC by down-regulating E-cadherin expression.
  • Snail promotes tumor invasion in HCC, independent of Slug.
  • Targeting Snail may offer a therapeutic strategy for inhibiting HCC progression and metastasis.

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