Zinc-finger transcription factor snail accelerates survival, migration and expression of matrix metalloproteinase-2 in human bone mesenchymal stem cells

Abstract

Although bone mesenchymal stem cells (BMSC) hold promise in gene therapy and tissue engineering, the inefficient migration and the low capability of subsequent survival of BMSC have largely restrained progress in these studies. Characteristics shared between stem cells and tumorigenic cells prompted us to investigate whether mechanisms of tumor progression contribute to stem cell migration. The transcription factor Snail which functions in epithelial-mesenchymal transitions (EMT) is responsible for the acquisition of motile and invasive properties of tumor cells. It is not yet known whether Snail acts in the mechanisms of stem cell migration. Here it is shown that ectopic Snail expression increased the migration of BMSC in vitro by a mechanism dependent on the phosphoinositide 3-kinase (PI-3K) signaling pathway. Snail expression may contribute to the constitutive activation of signaling pathways of PI-3K and MAPK and the related MMP-2 secretion in BMSC. Furthermore, the stem cells expressing Snail were protected from the apoptosis triggered by serum deprivation. These results suggested the possibility for us to optimize the migration of BMSC toward infarcted tissues and their subsequent survival in the local microenvironment, by investigating mechanisms associated with the acquisition of invasiveness by tumor cells.