Ganglioside GD3 induces convergence and synergism of adhesion and hepatocyte growth factor/Met signals in melanomas.
Bottom Line: In this study, we analyzed the effects of GD3 expression on cell signals triggered by hepatocyte growth factor (HGF)/Met interaction and by adhesion to collagen type I (CL-I).When resistance to induced apoptosis by H2O2 was examined, only GD3+ cells treated with both HGF and adhesion to CL-I showed clearly low percentages of dead cells compared with GD3- cells or GD3+ cells treated with either one of the stimulants.Cell growth measured by 5-ethynyl-2' deoxyuridine uptake also showed synergistic effects in GD3+ cells.
Affiliation: Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai, Japan; Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya, Japan.Show MeSH
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Mentions: We analyzed phosphorylation of Akt (p-Ser473, p-Thr308) by either HGF stimulation or adhesion to CL-I, or both of them at the same time in GD3+ cells and GD3− cells. The cells were harvested after starving for 14–16 h in serum-free DMEM and rotated for 1 h at 37°C to reduce basal phosphorylation levels of Akt. After HGF stimulation, phosphorylation of Ser473 in Akt was slightly higher in GD3+ cells, but phosphorylation of Thr308 in Akt was not different between GD3+ and GD3− cells (Fig.3A). Phosphorylation of Ser473 and Thr308 of Akt was higher in GD3+ cells than in GD3− cells during adhesion to CL-I, corresponding with our previous report,22 while the phosphorylation levels were low (Fig.3B). Then, we analyzed phosphorylation of Akt during costimulation of GD3+ and GD3− cells with HGF and adhesion to CL-I. Consequently, phosphorylation levels of Ser473 and Thr308 of Akt were definitely higher in GD3+ cells than in GD3− cells (Fig.3C). These results suggested that phosphorylation of Akt was synergistically enhanced by costimulation with HGF and adhesion to CL-I in GD3+ cells.
Affiliation: Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai, Japan; Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya, Japan.