The Advantages for Snail Expression to Promote Cell Migration and Induce Actin Reorganization and to Protect Against the Serum-deprivation-triggered Apoptosis of Bone Marrow Stem Cells

Abstract:

The Snail transcription factor has been described as a strong repressor of E-cadherin and its stable expression induces epithelial-mesenchymal transitions responsible for the acquisition of motile and invasive properties during tumor progression. A fascinating analogy that has been raised is the seemingly similar and shared characteristics of stem cells and tumorigenic cells，which prompted us to investigate whether the mechanisms of the acquisition of invasiveness during tumor progression are also involved in bone marrow stem cells(MSCs). In this study，we examined whether Snail gene expression acts in the mobility，cytoskeleton and anti-apoptosis of MSCs. Cell Transmigration Assay and Western Blotting were performed to evaluate the cell migratory capability and the related Signaling pathways in MSCs transfected with the Snail expression vector of pCAGGSneo-Snail-HA (MSCs-Sna)，compared with MSCs(MSCs-neo) transducted with the control vector(pCAGGSneo). Actin cytoskeleton by Immunofluorescence and Sub-G1 detection by a FACScan flow cytometer were performed to analyze the cytoskeleton and anti-apoptotic capability of MSCs-Sna. Compared with MSCs-neo，MSCs-Sna show significantly more migration in the transwell migration system (P<0.05). And suppression of PI-3K activation by the specific PI-3K inhibitor，Wortmannin，brought on a reduction in Snail-mediated MSCs migration. In addition，we provide evidences that high expression of Snail inhibited the serum-deprivation triggered apoptosis and cytoskeleton changement of MSCs. These data suggest the possibility of facilitating MSCs migration to injured tissue and subsequent survival and maintenance in the local microenvironment after their transplantation，by investigating and increasing the advantage factors such as Snail high expression in MSCs.