Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044, China; Department of Clinical Biochemistry, College of Laboratory Medicine, Dalian Medical University, Dalian 116044, China.
J Cell Biochem. 2013 Jul;114(7):1616-24. doi: 10.1002/jcb.24503.
Two related sublines derived from murine ascites hepatoma cell lines Hca-F25, which were selected for their markedly different metastatic potential to lymph nodes, were found to be distinct in their ganglioside patterns. The low metastatic cell line (HcaP) contained a major ganglioside GM3, whereas the high metastatic cell line (HcaF) contained a major ganglioside GM2. Suppression of GM3 by P4 enhanced the mobility and migration of the low metastatic HcaP cells in vitro. Increase in GM3 content in high metastatic HcaF cells by addition of exogenous GM3 inhibited the mobility and migration. These results suggested that the differences in lymphatic metastasis potential between these two cell lines could be attributed to the differences in their ganglioside compositions, and GM3 could suppress the motility and migration of these cells. Further, we investigated the mechanism by which GM3 suppressed the cell mobility and migration. The results showed that suppression of GM3 synthesis by P4 in low metastatic HcaP cells promoted PKB/Akt phosphorylation at Ser473 and Thr308, and phosphorylation of EGFR at the Tyr1173. In contrast, increase in GM3 content in high metastatic HcaF cells by addition of exogenous GM3 into the culture medium suppressed phosphorylation of PKB/Akt and EGFR at the same residues. Taken together, these results suggested that the mechanism of GM3-suppressed cell motility and migration may involve the inhibition of phosphorylation of EGFR and the activity of PI3K/AKT signaling pathway.
从具有明显不同淋巴结转移潜能的鼠腹水肝癌细胞系 Hca-F25 中分离出两个相关的亚系，发现它们的神经节苷脂图谱明显不同。低转移性细胞系 (HcaP) 含有主要的神经节苷脂 GM3，而高转移性细胞系 (HcaF) 含有主要的神经节苷脂 GM2。P4 对 GM3 的抑制作用增强了低转移性 HcaP 细胞在体外的迁移能力。通过添加外源性 GM3 增加高转移性 HcaF 细胞中 GM3 的含量，抑制了细胞的迁移能力。这些结果表明，这两个细胞系之间淋巴转移潜能的差异可能归因于它们神经节苷脂组成的差异，GM3 可以抑制这些细胞的运动和迁移。此外，我们研究了 GM3 抑制细胞迁移能力的机制。结果表明，低转移性 HcaP 细胞中 P4 抑制 GM3 合成可促进 PKB/Akt 在 Ser473 和 Thr308 处的磷酸化，以及 EGFR 在 Tyr1173 处的磷酸化。相比之下，通过在培养基中添加外源性 GM3 增加高转移性 HcaF 细胞中的 GM3 含量，可抑制 PKB/Akt 和 EGFR 在相同残基处的磷酸化。总之，这些结果表明 GM3 抑制细胞迁移和迁移的机制可能涉及抑制 EGFR 的磷酸化和 PI3K/AKT 信号通路的活性。
