Roles of glycosphinglipids in converging process of the cell signals of proliferation and adhesion in cancer cells.

本研究通过在GD 3+人黑色素瘤细胞膜附近形成分子复合物，研究了神经节苷脂GD 3在肿瘤细胞增殖和粘附信号汇聚过程中的作用，发现GD 3在胎牛血清刺激后，可增强FAK、p130 Cas和桩蛋白的酪氨酸磷酸化，从而促进黑色素瘤细胞的增殖和侵袭。除了通过生长因子/受体的信号外，通过整合素的粘附信号也可能被GD 3增强。本文研究了整合素介导的信号传导在细胞增殖和侵袭中的作用，以及整合素β1在衔接分子活化中的作用，表明整合素β1在细胞生长和侵袭中也起重要作用。FAK、p130 Cas和桩蛋白在无血清条件下与I型胶原的粘附过程中，GD 3+细胞比GD 3-细胞经历更强的酪氨酸磷酸化。此外，在膜附近的GD 3激活的分子进行了搜索。在黑色素瘤细胞系中表达的Src家族激酶（SFKs）中，只有Yes参与细胞增殖和侵袭等恶性特性，因此，在GD 3+细胞中，整合素参与细胞的生长和侵袭，并且在细胞粘附过程中观察到与FCS处理的细胞中检测到的类似的FAK、p130 Cas和桩蛋白的激活。这些结果表明，神经节苷脂GD 3在细胞增殖和粘附两条主要信号通路的会聚过程中起重要作用，导致GD 3+人黑素瘤细胞膜附近FAK、p130 Cas和桩蛋白的强烈激活。在细胞膜附近。

In this study, we have investigated the roles of ganglioside GD3 in converging process of the cell signals of proliferation and adhesion in cancer cells by forming molecular complex in the vicinity of cell membrane in GD3+human melanoma cells.We reported that ganglioside GD3 enhances cell proliferation and invasion of melanomas causing stronger tyrosine-phosphorylation of FAK, p130Cas and paxillin after stimulation with fetal calf serum. Besides signals via growth factor/receptor, adhesion signals via integrin might be also enhanced by GD3. Here, roles of integrin-mediated signaling in the cell proliferation and invasion, and in the activation of adaptor molecules were examined, showing that integrin β1 was also important for the cell growth and invasion. FAK, p130Cas and paxillin underwent stronger tyrosine-phosphorylation in GD3+ cells than in GD3- cells during the adhesion to collagen type I in the absence of serum. Furthermore, molecules activated by GD3 in the vicinity of membranes were searched. Among Src family kinases (SFKs), i.e. Yes, Src and Fyn expressed in the melanoma cell lines, only Yes was involved in the malignant properties such as cell proliferation and invasion.Consequently, in GD3+ cells, it was demonstrated that integrins are involved in cell growth and invasion, and similar activation of FAK, p130Cas and paxillin during cell adhesion to those detected in FCS-treated cells was observed. These results suggest that ganglioside GD3 is important for converging process of the two major signaling pathways for cell proliferation and adhesion leading to strong activation of FAK, p130Cas and paxillin in the vicinity of cell membrane in GD3+ human melanoma cells.Now, we are investigating the molecular mechanisms for the triggering of the conversion of the signals for cell proliferation and adhesion by GD3, in the vicinity of cell membrane.