Abstract 3916: The effect of snail on cellular adhesion in prostate cancer cells

Abstract

Abstract Purpose: The purpose of the study is to determine the role of Snail transcription factor on cellular adhesion to fibronectin and collagen, in human prostate cancer cells. Background: Cell adhesion plays an integral role in cell communication and regulation, subsequently it is of fundamental importance in the development and maintenance of tissue architecture. The adhesion process is involved in stimulating signals that regulate cellular differentiation, cell cycle, and cell survival. Adhesion of cells to one another or to the extracellular matrix (ECM) is responsible for a wide array of normal and abnormal cellular activity, such as a cell migration, invasion, metastasis of tumor cells, and angiogenesis. Integrins are receptor proteins that play an important role in cellular signaling and can bind a wide range of ligands for example vitronectin, collagen, fibronectin and laminin. Proteins such as Src, Erk and FAK play a crucial role in cell signaling and can be activated by integrins leading to activation of cellular pathways inside the cell. Snail transcription factor induces epithelial-mesenchymal transition (EMT) in which the epithelial cells loose their expression of specific genes, such as E-Cadherin, that codes for cell-to-cell adhesion and acquire traits of loosely associated mesenchymal genes, such as vimentin expression leading to increased invasion and migration. In order for cancer cells to metastasize, they must first detach from their extracellular matrix. Very little is known about the role of Snail in cellular adhesion. We hypothesized that Snail will lead to decreased cellular adhesion to fibronectin and collagen matrix, concomitant with increased cell migration. Methods: We stably overexpressed Snail in androgen dependent LNCaP (LNCaP-Snail) and androgen independent ArCaP (ARCaP-Snail) prostate cancer cells using lipofectamine 2000, or stably knocked down Snail in androgen-independent C4-2 and ARCaP-Snail cells using shRNA. We performed cell adhesion and migration assays on fibronectin and collagen I matrices using these cell models, and also performed RT-PCR to evaluate expression of fibronectin and collagen. Results: We found that ARCaP prostate cancer cells transfected with Snail displayed decreased adhesion to fibronectin and collagen I, which was reversed by Snail knockdown. Additionally we have seen a decrease in expression of fibronectin and collagen I in the cells lines over expressing Snail by RT-PCR, concomitant with increased migration on collagen. Conclusion: We have shown that Snail decreases cell adhesion to fibronectin and collagen, and inversely increases cell migration. Additionally, Snail leads to decreased expression of fibronectin and collagen mRNA. These studies define a new role for Snail transcription factor in cell adhesion to specific matrices like fibronectin and collagen that may be crucial for cell detachment and subsequent metastasis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3916.