Role of TGF­ß in the motility of ShcD­overexpressing 293 cells.

The newly identified Src homology and collagen (Shc) family member ShcD was observed to be upregulated in 50% of vertical growth phase and metastatic melanomas. The aim of the present study was to investigate the mechanism by which ShcD mediates cell motility. 293 cell lines were altered to stably express GFP (GF) or GFP­ShcD (G5). Treatment of the cells with transforming growth factor (TGF)ß2 promoted extracellular signal­regulated kinase (ERK) phosphorylation and, to a lesser extent, Smad2 phosphorylation in GFP­ShcD­expressing cells but not in GFP­overexpressing cells. GFP­ShcD­expressing cells exhibited upregulated expression of certain epithelial­mesenchymal transition­related genes, such as snail family transcriptional repressor 1 and SLUG, than GFP­expressing cells. Higher levels of ERK were found in the nuclear fraction of GFP­ShcD­expressing cells than that of GFP­expressing cells. Overall, GFP­ShcD­expressing cells demonstrated enhanced migration compared with GFP­expressing cells. A slight increase in cell migration was observed in both cell lines (GF and G5) when the cells were allowed to migrate towards conditioned medium derived from TGFß2­treated GFP­ShcD expressing cells. Collectively, ShcD upregulation was proposed to induce cell migration by affecting the expression of certain epithelial­mesenchymal transition­related genes. Thus, our findings may improve understanding of the role of ShcD in cell migration.