Ganglioside GD3 induces convergence and synergism of adhesion and hepatocyte growth factor/Met signals in melanomas.

Abstract

Ganglioside GD3 is highly expressed in human melanomas and enhances malignant properties of melanomas, such as cell proliferation and invasion activity. 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). Although stimulation of melanoma N1 cells (GD3+ and GD3-) with either HGF or adhesion to CL-I did not show marked differences in the phosphorylation levels of Akt at Ser473 and Thr308 between two types of cells, simultaneous treatment resulted in definite and markedly increased activation of Akt in GD3+ cells. Similar increases were also shown in Erk1/2 phosphorylation levels with the costimulation in GD3+ cells. 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. These results suggested that GD3 plays a crucial role in the convergence of multiple signals, leading to the synergistic effects of those signals on malignant properties of melanomas.

• Authors: Keiko Furukawa, Mariko Kambe, Maiko Miyata, Yuki Ohkawa, Orie Tajima, Koichi Furukawa
• Journal: Cancer science (Cancer Sci) Vol. 105 Issue 1 Pg. 52-63 (Jan 2014) ISSN: 1349-7006 [Electronic] England
• PMID: 24372645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Chemical References

• Collagen Type I
• Gangliosides
• HGF protein, human
• ganglioside, GD3
• Hepatocyte Growth Factor
• MET protein, human
• Proto-Oncogene Proteins c-met
• Proto-Oncogene Proteins c-akt

Topics

• Apoptosis (genetics)
• Cell Growth Processes (genetics)
• Cell Line, Tumor
• Collagen Type I (genetics, metabolism)
• Gangliosides (biosynthesis, genetics, metabolism)
• Hepatocyte Growth Factor (genetics, metabolism)
• Humans
• MAP Kinase Signaling System
• Melanoma (genetics, metabolism, pathology)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Proto-Oncogene Proteins c-met (genetics, metabolism)
• Signal Transduction