Open AccessGanglioside GD 3 induces convergence and synergism of adhesion and hepatocyte growth factor/Met signals in melanomas
Author(s) -
Furukawa Keiko,
Kambe Mariko,
Miyata Maiko,
Ohkawa Yuki,
Tajima Orie,
Furukawa Koichi
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12310
Subject(s) - hepatocyte growth factor , chemistry , phosphorylation , adhesion , protein kinase b , c met , apoptosis , cancer research , cell adhesion , growth factor , cell growth , microbiology and biotechnology , biology , biochemistry , receptor , organic chemistry
Ganglioside GD 3 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 GD 3 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 ( GD 3+ and GD 3−) 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 GD 3+ cells. Similar increases were also shown in Erk1/2 phosphorylation levels with the costimulation in GD 3+ cells. When resistance to induced apoptosis by H 2 O 2 was examined, only GD 3+ cells treated with both HGF and adhesion to CL ‐I showed clearly low percentages of dead cells compared with GD 3− cells or GD 3+ cells treated with either one of the stimulants. Cell growth measured by 5‐ethynyl‐2‘ deoxyuridine uptake also showed synergistic effects in GD 3+ cells. These results suggested that GD 3 plays a crucial role in the convergence of multiple signals, leading to the synergistic effects of those signals on malignant properties of melanomas.