Department of Biochemistry and Molecular Biology, Fudan University, Shanghai, PR China.
Arch Biochem Biophys. 2010 Oct 15;502(2):89-95. doi: 10.1016/j.abb.2010.07.014. Epub 2010 Jul 27.
Epidermal growth factor receptor variant III (EGFRvIII), the most common EGFR mutation, is associated with cell migration of glioblastoma multiforme (GBM) cases; however, the mechanism has not been elucidated. In this study, we found that the EGFRvIII-promoted glioma cell migration was closely linked to high levels of tyrosine phosphorylation in focal adhesion kinase (FAK) Y397. We also demonstrated that EGFRvIII formed a complex with FAK, resulting in enhanced tyrosine phosphorylation levels of FAK Y397 and EGFR Y1068. After knockdown of FAK expression via anti-FAK shRNA, the U87ΔEGFR cell migration was significantly inhibited, accompanying with the reduced phosphorylation levels of extracellular signal-regulated kinase (ERK1/2). Furthermore, the role of ERK1/2 in FAK-regulated cell migration was confirmed. Taken together, our results suggest that FAK and its downstream molecule ERK were involved in EGFRvIII-promoted glioma cell migration in U87ΔEGFR cells.
表皮生长因子受体变体 III（EGFRvIII）是最常见的 EGFR 突变，与多形性胶质母细胞瘤（GBM）病例的细胞迁移有关；然而，其机制尚未阐明。在这项研究中，我们发现 EGFRvIII 促进神经胶质瘤细胞迁移与粘着斑激酶（FAK）Y397 处的高酪氨酸磷酸化水平密切相关。我们还证明 EGFRvIII 与 FAK 形成复合物，导致 FAK Y397 和 EGFR Y1068 的酪氨酸磷酸化水平增强。通过抗 FAK shRNA 敲低 FAK 表达后，U87ΔEGFR 细胞迁移显著受到抑制，伴随着细胞外信号调节激酶（ERK1/2）的磷酸化水平降低。此外，还证实了 ERK1/2 在 FAK 调节细胞迁移中的作用。总之，我们的研究结果表明，FAK 及其下游分子 ERK 参与了 U87ΔEGFR 细胞中 EGFRvIII 促进的神经胶质瘤细胞迁移。
