Abstract
The function of Snail2 in mesenchymal tumors is, to date unknown. Using knockdown and overexpression studies, we show that Snail2 regulates migration and invasion of osteosarcoma cells. Knockdown resulted in significantly decreased motility, remodelling of the actin cytoskeleton, and loss of cellular protrusions. Over-expression increased motility, formation of actin-rich cellular protrusions, and altered expression of some non-canonical Wnt pathway components whilst decreasing expression of the adhesion molecule OB-cadherin. Unexpectedly, knockdown also resulted in significantly smaller tumors in an in vivo CAM assay. Therefore Snail2 may be a potential therapeutic target for clinical intervention of osteosarcoma.
Highlights
In epithelial tumor types the functions of the Snail zinc finger transcriptional repressors have been extensively studied [1]
The mechanism of action is similar, utilizing transcriptional repression of epithelial cellular adhesion molecules, including E-cadherin, allowing cells to break their cell to cell contacts [3,4,5], which is an early step in the process of epithelial-to-mesenchymal transition (EMT)
We demonstrated that Snail2 is expressed in long bone canine osteosarcomas; tumors of mesenchymal origin [7]
Summary
In epithelial tumor types (e.g. breast, lung and ovarian) the functions of the Snail zinc finger transcriptional repressors have been extensively studied [1]. In this context, the key function of Snail is similar to its function in embryonic epithelial tissues, namely the promotion of epithelial-to-mesenchymal transition (EMT) [2]. The mechanism of action is similar, utilizing transcriptional repression of epithelial cellular adhesion molecules, including E-cadherin, allowing cells to break their cell to cell contacts [3,4,5], which is an early step in the process of EMT. During embryonic development Snail is present in one tissue of mesenchymal origin, namely the developing long bone [6]. Expression is lost with age and in post-natal bone in vivo, Snail is absent (unpublished observations)
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