Open AccessGM1 / GD1b / GA1 synthase expression results in the reduced cancer phenotypes with modulation of composition and raft‐localization of gangliosides in a melanoma cell line
Author(s) -
Dong Yu,
Ikeda Kazutaka,
Hamamura Kazunori,
Zhang Qing,
Kondo Yuji,
Matsumoto Yasuyuki,
Ohmi Yuhsuke,
Yamauchi Yoshio,
Furukawa Keiko,
Taguchi Ryo,
Furukawa Koichi
Publication year - 2010
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/j.1349-7006.2010.01613.x
Subject(s) - raft , lipid raft , ganglioside , biology , tyrosine phosphorylation , cell culture , biochemistry , transfection , phosphorylation , chemistry , microbiology and biotechnology , cell , genetics , organic chemistry , copolymer , polymer
Gangliosides are expressed in neuroectoderm‐derived tumors, and seemed to play roles in the regulation of cancer properties. To examine the behavior and roles of individual gangliosides, GM1/GD1b/GA1 synthase cDNA was introduced into the melanoma cell line SK‐MEL‐37, and changes in tumor phenotypes were analyzed. The transfectant cells showed neo‐expression of GD1b, GT1b, and GM1, and reduced expression of GM3, GM2, GD2, and GD3. Function analyses revealed that the transfectant cells had definite reduction in cell growth and invasion. Tyrosine‐phosphorylation levels of proteins such as p130Cas and paxillin were also reduced in the transfectants. These results suggested that the expression of GM1/GD1b/GA1 synthase resulted in the suppression of tumor properties. In the analyses of the floating patterns of gangliosides using fractions from sucrose density gradient ultracentrifugation of TritonX‐100 extracts, the majority of gangliosides were found in glycolipid‐enriched microdomain (GEM)/raft fractions, while GD3, GD1b, and GT1b in the transfectant cells tended to disperse to non‐GEM/raft fractions. Furthermore, GD3, GD1b, and GT1b in non‐GEM/raft dominantly had unsaturated fatty acids, while those in GEM/rafts contained more saturated forms than in non‐GEM/rafts. This might be a mechanism for the decreased tumor properties in the transfectants of GM1/GD1b/GA1 synthase cDNA. ( Cancer Sci 2010)