Deregulation of Snai2 is associated with metastasis and poor prognosis in tongue squamous cell carcinoma

Int J Cancer. 2012 May 15;130(10):2249-58. doi: 10.1002/ijc.26226. Epub 2011 Aug 16.

Abstract

The members of the Snail superfamily of zinc-finger transcription factors, including Snai1 and Snai2, are involved in essential biological processes, such as epithelial-mesenchymal transition (EMT). Although Snai1 has been investigated in a number of cancers, our knowledge on Snai2 and its role(s) in squamous cell carcinoma of oral tongue (SCCOT) is limited. In this study, we confirmed the previous observation that over-expression of Snai2 is a frequent event in SCCOT. We further demonstrated that Snai2 over-expression is associated with lymph node metastasis in two independent SCCOT patient cohorts (total n = 129). Statistical analysis revealed that Snai2 over-expression was correlated with reduced overall survival. Furthermore, over-expression of Snai2 was correlated with reduced E-cadherin expression and enhanced Vimentin expression, suggesting a functional role of Snai2 in EMT. These observations were confirmed in vitro, in which knockdown of Snai2 induced a switch from a mesenchymal-like morphology to an epithelial-like morphology in SCCOT cell lines, and suppressed the cell invasion and migration. In contrast, ectopic transfection of Snai2 led to enhanced cell invasion and migration. Furthermore, Snai2 knockdown attenuated TGFβ1-induced EMT in SCCOT cell lines. Taken together, these data suggest that Snai2 plays major roles in EMT and the progression of SCCOT and may serve as a therapeutic target for patients at risk of metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Snail Family Transcription Factors
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / metabolism*
  • Tongue Neoplasms / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Vimentin / metabolism

Substances

  • Cadherins
  • SNAI1 protein, human
  • SNAI2 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors
  • Vimentin