Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya, Japan,
Glycoconj J. 2012 Dec;29(8-9):579-84. doi: 10.1007/s10719-012-9423-0. Epub 2012 Jul 5.
Sialic acid-containing glycosphingolipids, gangliosides are highly expressed in human cancer cells and regulate cell signals transduced via membrane microdomains. Generally, disialyl gangliosides enhance tumor phenotypes, while monosialyl gangliosides suppress them. In particular, gangliosides GD3 and GD2 are highly expressed in melanomas and small cell lung cancer cells, and their expression cause increased cell growth and invasion. In osteosarcomas, expression of GD3 and GD2 also enhanced cell invasion and motility, and caused increased phosphorylation of focal adhesion kinase and paxillin. In addition to focal adhesion kinase, Lyn kinase was also activated by GD3/GD2 expression, leading to the phosphorylation of paxillin. In contrast with melanoma cells, osteosarcomas showed reduced cell adhesion with increased phosphorylation of paxillin. Thus, increased expression of GD3/GD2 caused enhanced activation of signaling molecules, leading to distinct phenotypes between melanomas and osteosarcomas, i.e. increased and decreased adhesion activity. Thus, whole features of glycolipid-enriched microdomain/rafts formed in the individual cancer types seem to determine the main signaling pathway and biological outcome.
含有唾液酸的糖脂，即神经节苷脂，在人类癌细胞中高度表达，并调节通过膜微区转导的细胞信号。通常，双唾液酸神经节苷脂增强肿瘤表型，而单唾液酸神经节苷脂则抑制它们。特别是，GD3 和 GD2 神经节苷脂在黑色素瘤和小细胞肺癌细胞中高度表达，它们的表达导致细胞生长和侵袭增加。在骨肉瘤中，GD3 和 GD2 的表达也增强了细胞侵袭和迁移，并导致黏着斑激酶和桩蛋白的磷酸化增加。除了黏着斑激酶外，Lyn 激酶也被 GD3/GD2 的表达激活，导致桩蛋白的磷酸化。与黑色素瘤细胞相反，骨肉瘤细胞的黏附性降低，同时桩蛋白的磷酸化增加。因此，GD3/GD2 的表达增加导致信号分子的激活增强，导致黑色素瘤和骨肉瘤之间表现出不同的表型，即黏附活性增加和减少。因此，个体癌症类型中富含糖脂的微区/筏的整体特征似乎决定了主要的信号通路和生物学结果。
