GM1/GD1b/GA1 synthase expression results in the reduced cancer phenotypes with modulation of composition and raft-localization of gangliosides in a melanoma cell line
GM1/GD1b/GA1 synthase expression results in the reduced cancer phenotypes with modulation of composition and raft-localization of gangliosides in a melanoma cell line
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DOI：
10.1111/j.1349-7006.2010.01613.x
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发表时间：
2010-09-01
期刊：
影响因子：
5.7
通讯作者：
Furukawa, Koichi
中科院分区：
文献类型：
--
作者：
Dong, Yu;Ikeda, Kazutaka;Furukawa, Koichi
神经节苷脂在神经外胚层衍生的肿瘤中表达，似乎在癌症特性的调节中发挥作用。为了检查各个神经节苷脂的行为和作用，将 GM1/GD1b/GA1 合酶 cDNA 引入黑色素瘤细胞系 SK-MEL-37，并分析肿瘤表型的变化。转染细胞显示 GD1b、GT1b 和 GM1 的新表达，以及 GM3、GM2、GD2 和 GD3 的表达减少。功能分析显示转染细胞的细胞生长和侵袭明显减少。转染子中 p130Cas 和桩蛋白等蛋白质的酪氨酸磷酸化水平也有所降低。这些结果表明 GM1/GD1b/GA1 合酶的表达导致肿瘤特性的抑制。在使用 TritonX-100 提取物的蔗糖密度梯度超速离心馏分对神经节苷脂的漂浮模式进行分析时，发现大多数神经节苷脂存在于富含糖脂的微域 (GEM)/raft 馏分中，而转染细胞中的 GD3、GD1b 和 GT1b 倾向于分散到非 GEM/raft 馏分中。此外，非 GEM/raft 中的 GD3、GD1b 和 GT1b 主要含有不饱和脂肪酸，而 GEM/raft 中的 GD3、GD1b 和 GT1b 比非 GEM/raft 中含有更多的饱和脂肪酸。这可能是 GM1/GD1b/GA1 合酶 cDNA 转染子肿瘤特性降低的机制。 （癌症科学 2010）。
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).