Department of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.
Mol Cell Biochem. 2013 Oct;382(1-2):83-92. doi: 10.1007/s11010-013-1720-9. Epub 2013 Jun 8.
Ganglioside GM3 plays a well-documented and important role in the regulation of tumor cell proliferation, invasion, and metastasis by modulating tyrosine kinase growth factor receptors. However, the effect of GM3 on the hepatocyte growth factor receptor (HGFR, cMet) has not been fully delineated. In the current study, we investigated how GM3 affects cMet signaling and HGF-stimulated cell motility and migration using three hepatic cancer cell lines of mouse (Hca/A2, Hca/16A3, and Hepa1-6). Decreasing GM3 expression with the use of P4, a specific inhibitor for ganglioside synthesis inhibited the HGF-stimulated phosphorylation of cMet and activity of PI3K/Akt signaling pathway. In contrast, the increased expression of GM3 as a result of adding exogenous GM3 enhanced the HGF-stimulated phosphorylation of cMet and activity of PI3K/Akt signaling pathway. Furthermore, HGF-stimulated cell motility and migration in vitro were inhibited by reduced expression of GM3 and enhanced by increased expression of GM3. All the observations indicate that ganglioside GM3 promotes HGF-stimulated motility of murine hepatoma cell through enhanced phosphorylation of cMet at specific tyrosine sites and PI3K/Akt-mediated migration signaling.
神经节苷脂 GM3 通过调节酪氨酸激酶生长因子受体，在调节肿瘤细胞增殖、侵袭和转移方面发挥着重要作用。然而，GM3 对肝细胞生长因子受体（HGFR，cMet）的影响尚未完全阐明。在本研究中，我们使用三种小鼠肝癌细胞系（Hca/A2、Hca/16A3 和 Hepa1-6）研究了 GM3 如何影响 cMet 信号和 HGF 刺激的细胞迁移和运动。使用 P4（一种用于神经节苷脂合成的特异性抑制剂）降低 GM3 的表达，抑制了 HGF 刺激的 cMet 磷酸化和 PI3K/Akt 信号通路的活性。相比之下，由于添加外源性 GM3 而增加 GM3 的表达增强了 HGF 刺激的 cMet 磷酸化和 PI3K/Akt 信号通路的活性。此外，GM3 表达降低抑制了体外 HGF 刺激的细胞迁移和运动，而 GM3 表达增加则增强了这种迁移和运动。所有这些观察结果表明，神经节苷脂 GM3 通过增强 cMet 在特定酪氨酸位点的磷酸化和 PI3K/Akt 介导的迁移信号，促进 HGF 刺激的小鼠肝癌细胞的迁移。
