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Abstract 1550: The effect of snail on cellular adhesion in prostate cancer cells

Corey L. Neal, Danielle N. McKeithen, Valerie Odero‐Marah

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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. Adhesion of cells to one another or the extracellular matrix (ECM) is responsible for normal and abnormal cellular activity, such as cell migration, invasion, metastasis of tumor cells, and angiogenesis. Snail transcription factor induces epithelial-mesenchymal transition (EMT) in which epithelial cells loose expression of specific genes and acquire traits of mesenchymal genes. We hypothesized that Snail will lead to decreased cellular adhesion to fibronectin and collagen matrix, concomitant with increased cell migration. DESIGN METHODS: We stably overexpressed Snail in LNCaP (LNCaP-Snail) and ARCaP (ARCaP-Snail) prostate cancer cells, or stably knocked down Snail in 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. Flow cytometry was also used for integrin expression analysis. 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 the expression of the α5 and α2 integrin among ARCaP cell lines over expressing Snail, concomitant with an increased migration in cell lines overexpressing Snail. CONCLUSION: We have shown that Snail decreases cell adhesion to fibronectin and collagen, and inversely increases cell migration. These studies define a new role for Snail transcription factor that may be crucial for cell detachment and subsequent metastasis. Supported by grants P20MD002285-01 & G12RR003062-22 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1550. doi:10.1158/1538-7445.AM2011-1550

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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. Adhesion of cells to one another or the extracellular matrix (ECM) is responsible for normal and abnormal cellular activity, such as cell migration, invasion, metastasis of tumor cells, and angiogenesis. Snail transcription factor induces epithelial-mesenchymal transition (EMT) in which epithelial cells loose expression of specific genes and acquire traits of mesenchymal genes. We hypothesized that Snail will lead to decreased cellular adhesion to fibronectin and collagen matrix, concomitant with increased cell migration. DESIGN METHODS: We stably overexpressed Snail in LNCaP (LNCaP-Snail) and ARCaP (ARCaP-Snail) prostate cancer cells, or stably knocked down Snail in 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. Flow cytometry was also used for integrin expression analysis. 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 the expression of the α5 and α2 integrin among ARCaP cell lines over expressing Snail, concomitant with an increased migration in cell lines overexpressing Snail. CONCLUSION: We have shown that Snail decreases cell adhesion to fibronectin and collagen, and inversely increases cell migration. These studies define a new role for Snail transcription factor that may be crucial for cell detachment and subsequent metastasis. Supported by grants P20MD002285-01 & G12RR003062-22 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1550. doi:10.1158/1538-7445.AM2011-1550

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Available 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. Adhesion of cells to one another or the extracellular matrix (ECM) is responsible for normal and abnormal cellular activity, such as cell migration, invasion, metastasis of tumor cells, and angiogenesis. Snail transcription factor induces epithelial-mesenchymal transition (EMT) in which epithelial cells loose expression of specific genes and acquire traits of mesenchymal genes. We hypothesized that Snail will lead to decreased cellular adhesion to fibronectin and collagen matrix, concomitant with increased cell migration. DESIGN METHODS: We stably overexpressed Snail in LNCaP (LNCaP-Snail) and ARCaP (ARCaP-Snail) prostate cancer cells, or stably knocked down Snail in 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. Flow cytometry was also used for integrin expression analysis. 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 the expression of the α5 and α2 integrin among ARCaP cell lines over expressing Snail, concomitant with an increased migration in cell lines overexpressing Snail. CONCLUSION: We have shown that Snail decreases cell adhesion to fibronectin and collagen, and inversely increases cell migration. These studies define a new role for Snail transcription factor that may be crucial for cell detachment and subsequent metastasis. Supported by grants P20MD002285-01 & G12RR003062-22 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1550. doi:10.1158/1538-7445.AM2011-1550

Key concepts: Snail, Fibronectin, LNCaP, Biology, Cell adhesion, Extracellular matrix, Cell migration, Cell biology

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