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

鞘糖脂在癌细胞增殖和粘附的细胞信号汇聚过程中的作用。

• 批准号: 18590291
• 负责人: FURUKAWA Keiko
• 金额: $ 2.57万
• 依托单位: Chubu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590291/
• 关键词: glycosphinglipid; GD3; human melanoma; malignant phenotype; integrin; cell adhesion; extra-cellular matrix; Src family kinases; コラーゲン

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.

在这项研究中，我们通过在GD3+人黑色素瘤细胞的细胞膜附近形成分子复合体来研究神经节苷脂GD3在癌细胞增殖和黏附信号汇聚过程中的作用。我们报道了神经节苷脂GD3促进细胞增殖和黑色素瘤的侵袭，导致在胎牛血清刺激下FAK、p130Cas和paxlin的酪氨酸磷酸化增强。除了通过生长因子/受体的信号外，通过整合素的黏附信号也可能被GD3增强。本文对整合素介导的信号转导在细胞增殖和侵袭中的作用以及在接头分子激活中的作用进行了研究，表明整合素β1对细胞的生长和侵袭也很重要。在无血清的情况下，FAK、p130Cas和Paxlin在GD3+细胞与I型胶原黏附过程中发生了比GD3-细胞更强的酪氨酸磷酸化。此外，还寻找了膜附近被GD3激活的分子。在黑色素瘤细胞系中表达的Src家族激酶中，只有Yes参与了细胞的增殖和侵袭等恶性行为，因此，在GD3+细胞中，整合素被证实参与了细胞的生长和侵袭，并且在细胞黏附过程中观察到了FAK、p130Cas和paxlin的激活。这些结果表明，神经节苷脂GD3在细胞增殖和黏附的两个主要信号通路的汇聚过程中起重要作用，导致在GD3+的人黑色素瘤细胞中细胞膜附近FAK、p130Cas和paxlin的强烈激活。目前，我们正在研究GD3在细胞膜附近触发细胞增殖和黏附信号转换的分子机制。

项目成果

マウス肺癌転移におけるIntegrin及びRho制御分子の共同作用のメカニズム

整合素与Rho调控分子联合作用在小鼠肺癌转移中的机制

• 发表时间: 2007
• 作者: Furukawa;K.;章 青
• 通讯作者: 章 青

Interaction of GD3 with functional molecules in the vicinity of the cell membrane,leading to the malignant phenotypes of human melanomas

GD3与细胞膜附近功能分子的相互作用导致人类黑色素瘤的恶性表型

• 发表时间: 2006
• 作者: Furukawa;K.;章 青;山内祥生;Hamamura K.;Furukawa K.
• 通讯作者: Furukawa K.

GD3発現によるメラノーマの悪性形質形成におけるインテグリンの役割

GD3表达整合素在黑色素瘤恶性转化中的作用

• 发表时间: 2006
• 作者: Furukawa;K.;章 青;山内祥生;Hamamura K.;Furukawa K.;宮崎 清香
• 通讯作者: 宮崎 清香

Roles of glycolipids in the development and maintenance of nervous tissues.

糖脂在神经组织发育和维护中的作用。

• 发表时间: 2006
• 期刊: Methods Enzymol 417
• 作者: Furukawa;K.;et al.
• 通讯作者: et al.

Disruption of GM2/GD2 synthase resulted in overt expression of 9-O-acetyl GD3 irrespective of Tis21.

GM2/GD2 合酶的破坏导致 9-O-乙酰基 GD3 的明显表达，与 Tis21 无关。

• 发表时间: 2008
• 期刊: J. Neurochem. 105
• 作者: Furukawa;K.;et. al.
• 通讯作者: et. al.