Snail promotes an invasive phenotype in lung carcinoma

Heta Merikallio,Paavo Pääkkö,Kaarteenaho Riitta,Terttu Harju,Sirpa Salo,Riitta Mäkitaro,Tuula Salo,Ylermi Soini,Taina Turpeenniemi-Hujanen

doi:10.1186/1465-9921-13-104

Abstract

BackgroundSnail is a transcriptional factor which is known to influence the epitheliomesenchymal transition (EMT) by regulating adhesion proteins such as E-cadherin and claudins as well as matrix metalloproteases (MMP).MethodsTo evaluate the functional importance of snail, a transciptional factor involved in EMT in lung tumors, we investigated its expression in a large set of lung carcinomas by immunohistochemistry. Expression of snail and effects of snail knockdown was studied in cell lines.ResultsNuclear snail expression was seen in 21% of cases this being strongest in small cell lung carcinomas (SCLC). There was significantly greater snail expression in SCLC compared to squamous cell or adenocarcinoma. Positive snail expression was associated with poor survival in the whole material and separately in squamous cell and adenocarcinomas. In Cox regression analysis, snail expression showed an independent prognostic value in all of these groups. In several cell lines knockdown of snail reduced invasion in both matrigel assay and in the myoma tissue model for invasion. The influence of snail knockdown on claudin expression was cell type specific. Snail knockdown in these cell lines modified the expression of MMP2 and MMP9 but did not influence the activation of these MMPs to any significant degree.ConclusionsThe results show that snail plays an important role in the invasive characteristics of lung carcinoma influencing the survival of the patients. Snail knockdown might thus be one option for targeted molecular therapy in lung cancer. Snail knockdown influenced the expression of claudins individually in a cell-line dependent manner but did not influence MMP expressions or activations to any significant degree.

Highlights

Snail is a transcriptional factor which is known to influence the epitheliomesenchymal transition (EMT) by regulating adhesion proteins such as E-cadherin and claudins as well as matrix metalloproteases (MMP)
We studied the Messenger ribonucleic acid (mRNA) expression of snail in three cell lines, a transformed non-neoplastic bronchial cell line (BEAS-2B) and two neoplastic cell lines (SK-LU1, SK-MES1), determined their invasion properties by snail knockdown and the influence of snail knockdown on the expression of claudin mRNA expression as well as the expression and activation of MMPs 2 and 9
Snail appears to be important in the invasive nature of lung carcinomas which is shown by its impact on patient survival as well as in vitro invasion assay experiments

Summary

Introduction

Snail is a transcriptional factor which is known to influence the epitheliomesenchymal transition (EMT) by regulating adhesion proteins such as E-cadherin and claudins as well as matrix metalloproteases (MMP). It is believed that the activation of transcription factors, such as slug, snail or twist is responsible for EMT and downregulation of these adhesion molecules in epithelial cells [1,2]. Snail has been found to downregulate the expression of tight junction proteins occludin and claudins [1,6,7]. In this way snail regulates several genes which are involved in EMT. Snail influences apoptosis and cell movement and in this way may play a role in the spread of the tumor [3]

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